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TSP-1 up-regulated MMP-9 expression by AGS cells. Paper-9247692.
Neither TSP-1 nor TGF-beta1 had an effect on uPA production. Paper-8349075.
Thrombospondin-1 is a transcriptional repression target of PRMT6. Paper-14547337.
Such an action of TSP1 may account for the effect of HDAC inhibitors. Paper-12761944.
P123 competed for 125I- TSP1 incorporation into the fibrin clot. Paper-1708261.
Both OPN and TSP-1 specifically bind to IGFBP-5 with high affinity. Paper-2130741.
Transforming growth factor-beta complexes with thrombospondin. Paper-7406156.
Tissue factor pathway inhibitor binds to platelet thrombospondin-1. Paper-8628530.
Removal of bound Ca2+ from TSP1 reduces its binding to full-length TSG-6. Paper-10794403.
TFPI bound to immobilized TSP-1 remains an active proteinase inhibitor. Paper-8628530.
Inhibition of TSP-1 induced TIMP-1 levels increased tumor cell invasion. Paper-14152850.
CONCLUSION: TSP-1 on DMPhi could influence IL-10 expression as Th2 cytokines. Paper-13630383.
Thrombospondin protected fibronectin from cleavage by neutrophil elastase. Paper-7780803.
Thrombospondin is a tight- binding competitive inhibitor of neutrophil elastase. Paper-7780803.
The addition of IGFBP-5 (1.0 microg/ml) inhibited TS-1- IAP association. Paper-10766176.
The TSP-1- mediated stimulation of uPA appears to occur at post-transcriptional level. Paper-12842915.
Thrombospondin modulates alpha v beta 3 function through integrin-associated protein. Paper-739077.
Platelet thrombospondin interacts with plasminogen in a specific and saturable manner. Paper-6459159.
Hence, TGF-beta can bind to TSP, and the complex forms under physiological conditions. Paper-7406156.
Thrombospondin-1 inhibits in vitro megakaryocytopoiesis via CD36. Paper-10014349.
Neither RAP nor LRP antibodies inhibited the binding of 125I- TSP1 to surfaces of SMCs. Paper-249770.
Thrombospondin- fibronectin interaction is also inhibited by soluble thrombospondin. Paper-4809099.
The aim of the present study was to identify region(s) of TSP involved in binding of GPIIIb. Paper-61743.
Finally, TSP1 is also secreted by fibroblasts in response to Epac/ Rap1 activation. Paper-14145632.
Androgen receptor targets NFkappaB and TSP1 to suppress prostate tumor growth in vivo. Paper-13300768.
Histidine-rich glycoprotein inhibits the antiangiogenic effect of thrombospondin-1. Paper-8689729.
Expression of TSP-1 was markedly enhanced in hepatic HuH-7 cells by EGF but not by TGFbeta1. Paper-9432656.
Scatter factor binds to thrombospondin and other extracellular matrix components. Paper-664762.
Furthermore, vWF in solution at normal plasma levels also inhibited RBC adhesion to immobilized TSP. Paper-954197.
Thrombospondin was found to specifically bind to plasminogen and the nonenzyme chain of plasmin. Paper-6459159.
IL-18 enhances thrombospondin-1 production in human gastric cancer via JNK pathway. Paper-11999176.
COMP is a secreted pentameric glycoprotein that belongs to the thrombospondin family of proteins. Paper-8894503.
The data indicates that cell surface proteoglycans are involved in the LRP- mediated clearance of TSP1. Paper-249770.
Fibroblast-stimulated MMP-9 production was comparable with TSP-1- stimulated MMP-9 production. Paper-9549213.
Introduction of wild-type p53 enhances thrombospondin-1 expression in human glioma cells. Paper-9875594.
The constitutively active form of AhR induced activation of the thrombospondin-1 gene promoter. Paper-12841998.
Tumor suppressor U19/ EAF2 regulates thrombospondin-1 expression via p53. Paper-14214851.
Therefore, the N-modules of both TSP1 and TSP2 specifically recognize the Link module of TSG-6. Paper-10794403.
Thrombospondin-1 inhibits nitric oxide signaling via CD36 by inhibiting myristic acid uptake. Paper-13239049.
Tissue plasminogen activator and urokinase enhance the binding of plasminogen to thrombospondin. Paper-5411521.
Thrombospondin-1 and ADAMTS13 competitively bind to VWF A2 and A3 domains in vitro. Paper-15454502.
Platelet thrombospondin forms a trimolecular complex with plasminogen and histidine-rich glycoprotein. Paper-5079045.
Pig CD47 was stably expressed on CHO cells and shown to bind human thrombospondin ( TSP). Paper-9526654.
A CD36- binding peptide from thrombospondin-1 can stimulate resorption by osteoclasts in vitro. Paper-8491742.
Thrombospondin 1 binding to calreticulin- LRP1 signals resistance to anoikis. Paper-13065497.
Additionally, TSP1 is unable to activate latent TGF-beta when VLAL is deleted from the mature domain. Paper-11424677.
However, U19/ EAF2 transfection alone had little or no effect on the TSP-1 promoter. Paper-14214851.
Gel shift and antibody supershift studies indicated that ATF-1 was involved in DNA binding to the TSP-1-CRE site. Paper-13247361.
The inhibition of adhesion by vWF was shown to be the result of specific and saturable binding of vWF to TSP. Paper-954197.
We observed that TSP1 partially blocked ADAMTS13 binding to A2 domain, A3 domain and full length VWF. Paper-15454502.
IL-18- enhanced TSP-1 expression was blocked by SP600125, a c-Jun N-terminal kinase (JNK) specific inhibitor. Paper-11999176.
VLAL peptide inhibits TSP1- mediated activation of recombinant and endothelial cell-derived latent TGF-beta. Paper-11424677.
TSP binding to a GPIIIb-affinity column was Ca(2+)-dependent and reduced by 45% in the presence of EDTA. Paper-61743.
E. Thrombospondin 1 binding to calreticulin- LRP1 signals resistance to anoikis. Paper-13065497.
TSP-1 and TGF-beta1 promoted a dose-dependent upregulation of ASPC-1 and COLO-357 PAI-1 expression. Paper-8349075.
We studied how CD36 affects the growth of the osteosarcoma cell line (HOS) expressing TSP1. Paper-10324001.
The p53 tumor suppressor gene inhibits angiogenesis by stimulating the production of thrombospondin. Paper-7916605.
Molecular mechanisms by which DCN interacts with TSP and inhibits cell adhesion to TSP are unknown. Paper-1212008.
We here show that calumenin in the presence of Ca(2+) binds to TSP1 with a dissociation constant K (d) around 0.4 muM. Paper-13493299.
Mature two-chain SF and precursor single-chain SF bound approximately equally well to TSP-1 and Fn. Paper-664762.
These results indicate that TSP-1 regulates the multimeric size and therefore hemostatic activity of vWF. Paper-8993305.
Human thrombospondin's ( TSP-1) C-terminal domain opens to interact with the CD-47 receptor: a molecular modeling study. Paper-12946788.
Only the induction of wild-type p53 enhanced expression of thrombospondin-1 mRNA and the protein in U-251 MG cells. Paper-9875594.
Thrombospondin-1 inhibits VEGF receptor-2 signaling by disrupting its association with CD47. Paper-15535539.
VWF reductase activity was present in the Ca(++)- binding repeats and C-terminal sequence of TSP-1, but not of TSP-2. Paper-9574251.
However, the CD47- activated SS RBC adhesion receptor(s) that mediated adhesion to immobilized TSP remained unknown. Paper-10627824.
In contrast, expression of TSP-1 was markedly enhanced by TGFbeta1, but not by EGF, in osteosarcoma MG63 cells. Paper-9432656.
TSP-1 and TGF-beta 1 induced a twofold increase on uPAR expression but only a slight increase on total uPA. Paper-1515843.
Solid-phase binding assays confirmed that LRP bound to TSP1 and that the interaction was of high affinity (Kd = 5 nM). Paper-249770.
CONCLUSIONS: This study shows that high expression of THBS 1 is associated with tumor invasiveness and progression in HCC. Paper-10440014.
Thrombospondin type 1 repeats interact with matrix metalloproteinase 2. Regulation of metalloproteinase activity. Paper-8628587.
Using a TSP-1 promoter reporter gene, we further show that PRMT6 directly regulates the TSP-1 promoter activity. Paper-14547337.
The high levels of beta-TG and PF4 in sera inhibited release of intracellular alpha-granule TSP in vitro. Paper-1484648.
Here we describe that TSP inhibits EC chemotactic response to basic fibroblast growth factor ( bFGF). Paper-11726951.
Furthermore, the MAPK signaling pathway is predominantly responsible for HGF- induced TSP-1 downregulation. Paper-14196924.
TSP promoted attachment but not spreading of MDA-MB-231 cells which attached and spread on FN and LN substrates. Paper-7870989.
Binding is inhibited by polyclonal antibodies against TFPI and partially inhibited by the B-7 monoclonal anti- TSP-1 antibody. Paper-8628530.
Thrombospondin-1- induced apoptosis of brain microvascular endothelial cells can be mediated by TNF-R1. Paper-13488437.
The anti-adhesive activity of thrombospondin is mediated by the N-terminal domain of cell surface calreticulin. Paper-9171542.
Results offer structural insight into the role of TSP1 binding to CRT in CRT-induced focal adhesion disassembly. Paper-15070052.
CONCLUSION: Dau inhibited redistribution of GPIV and release of intracellular alpha-granule thrombospondin induced by thrombin. Paper-2181827.
In this study we have demonstrated that purified human platelet TSP formed a trimolecular complex with human Plg and HRGP. Paper-5079045.
Previously we showed that thrombospondin-1 ( TSP-1) activates latent TGF-beta both in vitro and in vivo. Paper-8664278.
Interaction of TSP-1 with vWF is mediated by TSP-1 type 1 properdin domains and the vWF A3 domain. Paper-8993305.
In this study we have demonstrated that purified human platelet TSP formed a complex with purified human plasminogen ( Plg). Paper-4810289.
We consistently observed lower levels of TSP-1 in diabetic patients who expressed the higher-molecular-weight PEDF isoform. Paper-14532658.
Hepatocyte growth factor enhances ovarian cancer cell invasion through downregulation of thrombospondin-1. Paper-14196924.
HGF stimulation of cell invasion and enhancement of MMP-9 expression were partially suppressed by TSP-1 overexpression. Paper-14196924.
Anti- uPA and anti-uPAR antibodies completely blocked the TSP-1 and TGF-beta 1-mediated pancreatic tumor cell invasion. Paper-1515843.
PTX pretreatment inhibits TSP/hep I- mediated focal adhesion disassembly as well as PI3K activation. Paper-9163692.
T cell adhesion and aggregate formation on TSP1(+) FLS substrates are inhibited by CD47-binding peptides. Paper-9935051.
Blockade of the p38 MAPK pathway with the upstream inhibitor SB-203580 also abolished TGF-beta1- induced TSP-1 expression. Paper-11993479.
We investigated the mechanism by which TS- bound IAP modulates the affinity of platelet integrin, alphaIIbbeta3. Paper-9793392.
These data suggest that TSP can cross- link platelets and monocytes via an interaction with GPIV on the surface of both cells. Paper-6465824.
We now report that TSP-1 up-regulates TIMP-1 expression in both human breast and prostate cancer cell lines. Paper-14152850.
Prosaposin inhibits tumor metastasis via paracrine and endocrine stimulation of stromal p53 and Tsp-1. Paper-13786442.
Thrombospondin 1- induced migration is more dependent upon ERK1/2 and p38 than Fn- or Vn-included migration. Paper-15601537.
Cells that express IAP bind strongly to TS1, the CBD, and its active cell-binding peptides while IAP negative cells do not. Paper-464860.
Using ELISA, purified osteonectin binds to solid-phase-adsorbed thrombospondin with a dissociation constant (Kd) of 0.7 nM. Paper-6097048.
This peptide bound to 125I-active TGF-beta and inhibited interactions of TSP1 with latent TGF-beta. Paper-195312.
Hepatocyte growth factor/scatter factor mediates angiogenesis through positive VEGF and negative thrombospondin 1 regulation. Paper-10165189.
The binding of soluble thrombospondin to surface- bound fibrinogen is inhibited both by soluble fibronectin and soluble fibrinogen. Paper-4809099.
Tumour cell thrombospondin-1 regulates tumour cell adhesion and invasion through the urokinase plasminogen activator receptor. Paper-8397710.
A model for the clearance of TSP1 by these cells is that TSP1 bound to proteoglycans is presented to LRP for endocytosis. Paper-249770.
In this study, we have found that the TSP-1 receptors CD36 and beta1 integrin associate with the VEGF receptor 2 (VEGFR2). Paper-14024679.
A carboxyl terminal truncation mutant of CD36 is secreted and binds thrombospondin: evidence for a single transmembrane domain. Paper-8201085.
Expression of the angiogenesis inhibitor thrombospondin-1 ( TSP-1) is induced by TGF-beta via Smad-dependent p38 activation. Paper-9265766.
In contrast, a mutant form of IGFBP-5 that bound poorly to TS-1 had a minimal effect on TS-1 binding to IAP. Paper-10766176.
In solid phase binding assays, purified 125I- TSP1 bound to immobilized GST/ LIMPII in a time-dependent and saturable manner. Paper-1348052.
Use of a TSP-1-specific blocking peptide demonstrated that the ANG II- induced activation of latent TGF-beta1 operates via TSP-1. Paper-10235344.
Proliferative cytokines such as IL-6 and bFGF inhibit TSP secretion, whereas the anti-proliferative TGF-beta enhances it. Paper-1274228.
Thrombospondin-1 may modulate keloid formation through up-regulation of the matrix- associated plasminogen/plasmin system. Paper-9497048.
TGF-beta1 (5 ng/ml) induced phosphorylation of p38 MAPK and induced TSP-1 mRNA and protein expression in HCASMC. Paper-11993479.
To demonstrate that the TSP-1 inhibitory signal was mediated by CD36, we transduced CD36 in CD36-deficient endothelial cells. Paper-10979068.
Thrombospondin 1 protected fibronectin from cleavage by cathepsin G and blocked cathepsin G-mediated platelet aggregation. Paper-102069.
The expression of IL-10 was decreased significantly in DMPhi from controls when adding anti- TSP-1 antibody to culture medium ( P < 0.05). Paper-13630383.
Besides FGF-2, TSP-1 also inhibited VEGF and HGF/SF binding to the ECM and mobilized them from the ECM. Paper-10057771.
Integrin-associated protein ( IAP) is a receptor for the carboxyl-terminal "cell- binding domain" (CBD) of thrombospondin 1 ( TS1). Paper-739077.
Structural insight into the role of thrombospondin-1 binding to calreticulin in calreticulin-induced focal adhesion disassembly. Paper-15070052.
Thrombospondin-1 induces platelet activation through CD36-dependent inhibition of the cAMP/protein kinase A signaling cascade. Paper-15447526.
At saturation the relative molar stoichiometry of Plg:TPA was 3:1 within the TSP-containing complexes and 1:1 within HRGP-containing complexes. Paper-5126593.
We conclude residues Lys244-Pro254 on kininogen heavy chain is responsible for binding to thrombospondin on the surface of activated platelets. Paper-1332739.
We report on the mRNA and protein expression of TSP1/ CD36 / CD47-complex in IBM muscles and in human myoblasts after cytokine stimulation. Paper-13328330.
Here we demonstrate that the alpha4beta1 integrin (VLA-4) is the receptor that mediates CD47- stimulated SS RBC adhesion to immobilized TSP. Paper-10627824.
Recombinant mouse TSP2 inhibited BAE cell proliferation in response to LPA in a dose range similar to that of TSP1. Paper-888052.
TSP-1 treatment for 17 h induced caspase-3 cleavage that required caspase-8 activity and the tumor necrosis factor receptor 1 ( TNF-R1). Paper-13488437.
The TSP1/ CD36/ CD47-complex is involved in T cell expansion and inflammatory responses to beta-amyloid, both relevant to IBM. Paper-13328330.
The thrombospondin-1 N700S polymorphism is associated with early myocardial infarction without altering von Willebrand factor multimer size. Paper-12080093.
These studies indicate that GPIIIb binds to the TSP via the C-terminal region and/or the CSVTCG motif, but not to the N-terminal region. Paper-61743.
CD36 is a trans-membrane receptor that regulates apoptosis and angiogenesis in response to its ligand thrombospondin-1 ( TSP-1). Paper-10210583.
Because TSG-6 modulates CD44-mediated cellular interactions with hyaluronan, we examined the possibility that TSP1 interacts with TSG-6. Paper-10794403.
THBS 1 appears to be a proangiogenic factor that stimulates angiogenesis in HCC in view of its positive correlation with VEGF expression. Paper-10440014.
Jurkat cells transfected with CD36 cDNA express an 88kD membrane surface protein and acquire the ability to bind thrombospondin. Paper-7405374.
Kinetic analysis demonstrated a marked increase in the affinity of TPA for plasminogen in the presence of surface- associated TSP or HRGP. Paper-5126593.
We hypothesized that the FGF-2 binding sequence of TSP-1 might serve as a template for the development of inhibitors of angiogenesis. Paper-14276049.
Increased plasma thrombospondin-1 ( TSP-1) levels are associated with the TNF alpha-308A allele in children with juvenile dermatomyositis. Paper-9532514.
The cells were next treated with specific inhibitors in order to determine the signal pathway involved in IL-18- enhanced TSP-1 production. Paper-11999176.
Peptide inhibition of TGF-beta1 activation by TSP-1 in high-glucose conditions completely suppressed increases in FN and PAI-1 expression. Paper-8822424.
Calumenin but not reticulocalbin forms a Ca2+-dependent complex with thrombospondin-1. A potential role in haemostasis and thrombosis. Paper-13493299.
By contrast, the addition of an antibody against ECM proteins inhibited the effects of OPN and TSP-1 on IGFBP-5 expression. Paper-12629196.
Apparent Kd values were approximately 12-36 nM for the interaction of TPA with TSP- Plg complexes and 15-31 nM with HRGP- Plg complexes. Paper-5126593.
IGFBP-5 mutants that contained substitutions for basic residues in the 201-218 region were tested for their ability to bind to TSP-1 or OPN. Paper-2130741.
HRGP covalently cross- linked to Sepharose 4B simultaneously bound both 125I- TSP and 131I- Plg, confirming trimolecular complex formation. Paper-5079045.
ADAM with ThromboSpondin-like motifs ( ADAMTS) are secreted proteases characterised by thrombospondin ( TS) motifs in their C-terminal domain. Paper-10840804.
These data identify a novel mechanism whereby TSP-1 can inhibit angiogenesis-through induction of apoptosis in a process mediated by TNF-R1. Paper-13488437.
Electrophoretic mobility shift assay indicated that CCAAT-binding factor ( CBF) was specifically bound to the CCAAT box of TSP1 promoter. Paper-12761944.
The TSP- promoted production of PAI-1 could be inhibited not only by anti- TSP antibodies but also by a neutralizing antibody against TGF-beta. Paper-132528.
Thus, our findings represent the first demonstration that TSP-1 inhibits in vitro megakaryocytopoiesis via interaction with CD36. Paper-10014349.
Insulin-like growth factor binding protein-5 ( IGFBP-5) interacts with thrombospondin-1 to induce negative regulatory effects on IGF-I actions. Paper-10766176.
This effect was inhibited by antibodies against the type I repeat domain of TSP-1 further suggesting that TSP-1 mediates TIMP-1 secretion. Paper-14152850.
Thrombospondin binds and activates the small and large forms of latent transforming growth factor-beta in a chemically defined system. Paper-136507.
When the cells were cultured with 12-o-tetradecanoylphorbol-13-acetate (TPA), the expression of TSP was enhanced and vWF was also detected, but not Fbg. Paper-7873645.
In agreement, the obtained model of the open TSP-1 was further used for protein-protein docking experiments against a homology model generated for CD-47. Paper-12946788.
Integrin-associated protein ( IAP/ CD47) is a receptor for the C-terminal cell binding domain of thrombospondin ( TS). Paper-9793392.
We previously demonstrated that thrombospondin 1 ( TSP-1) up-regulates MMP-9 expression by endothelial cells and promotes tumor cell invasion. Paper-9247692.
Hepatocyte growth factor ( HGF) downregulates thrombospondin 1 ( TSP-1) expression in thyroid papillary carcinoma cells. Paper-11545323.
Glucose stimulation of transforming growth factor-beta bioactivity in mesangial cells is mediated by thrombospondin-1. Paper-8664278.
Thrombospondin synthesized and secreted by human endothelial cells in culture binds specifically to fibronectin immobilized on Sepharose beads. Paper-4809099.
Here, we show that, in the very same tumor cells, in addition to inducing VEGF expression, HGF/ SF dramatically down-regulates TSP-1 expression. Paper-10165189.
Co-expression of IAP and TSP-1 on human GC may suggest that TSP-1 has a physiological role in GC function possibly via IAP in an autocrine fashion. Paper-8291534.
HRGP colocalized with TSP-1 in the stroma of human breast cancer specimens, and this interaction masked the antiangiogenic epitope of TSP-1. Paper-8689729.
We showed that recombinant full-length human TSG-6 (TSG-6Q) and the Link module of TSG-6 (Link_TSG6) bind 125I- TSP1 with comparable affinities. Paper-10794403.
These results suggest that TSP by a mechanism involving TGF-beta can promote cell adhesion through stimulation of tumor cell secretion of PAI-1. Paper-132528.
However, both ligand blotting and solid phase binding studies indicate that this truncated fragment of TSP-1 retained high-affinity binding to LRP-1. Paper-10501412.
Aryl hydrocarbon receptor is activated by glucose and regulates the thrombospondin-1 gene promoter in endothelial cells. Paper-12841998.
In a competitive binding assay, cathepsin G bound to thrombospondin 1 reversibly and saturably with a dissociation constant in the low nanomolar range. Paper-102069.
Interestingly, ginsenoside Rg1 decreased the expression of TSP-1 and enhanced vascular endothelial growth factor ( VEGF) expression. Paper-15485223.
Moreover, two SF alpha-chain peptides (NK1 and NK2) both bound to TSP-1 and Fn, suggesting that the whole SF molecule is not required for binding. Paper-664762.
Both the internalization and degradation of 125I- TSP1 could be inhibited by a specific antagonist of the LDLR family, the 39-kD receptor-associated protein (RAP). Paper-249770.
Whether the proteins were first combined in solution or sequentially applied to the slide, the presence of vWF inhibited the binding of sickle RBC to TSP. Paper-954197.
These studies show that radiolabeled IGFBP-5 specifically coprecipitates with two ECM proteins, thrombospondin-1 ( TSP-1) and osteopontin ( OPN). Paper-2130741.
Thrombospondin-1 type 1 repeat recombinant proteins inhibit tumor growth through transforming growth factor-beta-dependent and -independent mechanisms. Paper-9088178.
Activation of latent TGF-beta by TSP stripped of associated TGF-beta activity (sTSP) is time- and concentration-dependent, but temperature-independent. Paper-136507.
It was reported that TSP1 might protected VWF from cleaving by ADAMTS13, yet the underlying mechanism of this VWF protection has remained unknown. Paper-15454502.
These results suggest that at least some growth modulating activities of TSP are due to TGF-beta associated with TSP by strong non-covalent forces. Paper-7406156.
Plg activators did not influence binding of Plg to histidine-rich glycoprotein or of histidine-rich glycoprotein to TSP, demonstrating specificity. Paper-5411521.
Low density lipoprotein receptor-related protein mediates endocytic clearance of pro-MMP-2.TIMP-2 complex through a thrombospondin-independent mechanism. Paper-10855532.
We now describe a more potent mechanism by which TSP1 inhibits VEGF receptor-2 ( VEGFR2) activation through engaging its receptor CD47. Paper-15535539.
This regulation depends on an intact EWS/FLI1 DNA- binding domain and may involve direct interactions between EWS/FLI1 and thrombospondin promoter regions. Paper-13342940.
Anti- TSP-1 receptor antibody blocked the TSP-1 effect on PAI-1 expression but had no effect on TGF-beta1- mediated PAI-1 expression. Paper-8349075.
We have previously shown that platelet-produced thrombospondin-1 up-regulates the urokinase plasminogen activator and its receptor and promotes tumour cell invasion. Paper-8397710.
Antibodies to the LDLR-related protein ( LRP) completely blocked the uptake and degradation of 125I- TSP1 in SMCs and fibroblasts but not endothelial cells. Paper-249770.
We have shown previously that HRGP binds with high affinity to thrombospondin-1 ( TSP-1), a homotrimeric glycoprotein that is a potent inhibitor of angiogenesis. Paper-8689729.
Fluvastatin abolished TGF-beta1- induced phosphorylation of p38 MAPK and TGF-beta1- induced TSP-1 expression. Paper-11993479.
Here we show that CD36 triggered by TSP-1 inhibits in vitro angiogenesis stimulated by vascular endothelial growth factor-A ( VEGF-A). Paper-10979068.
In contrast to these factors, interferon-gamma ( INF-gamma) inhibits KC production of both FN and TSP and concomitantly inhibits both motility and proliferation. Paper-6108902.
Consistent with this mechanism, activation of Epac/Rap 1 induces expression of TSP1; conversely, depletion of Epac reduces TSP1 levels in endothelial cells. Paper-14145632.
Thrombospondin- bound integrin-associated protein ( CD47) physically and functionally modifies integrin alphaIIbbeta3 by its extracellular domain. Paper-9793392.
Endogenous TSP-1 is attached to lipoprotein receptor-related protein 1 (LRP1/CD91) and calreticulin ( CRT) on the cell surface through its NH2-terminal domain. Paper-12281880.
The tryptophan-rich motifs of the thrombospondin type 1 repeats bind VLAL motifs in the latent transforming growth factor-beta complex. Paper-11424677.
Thus, platelets containing 1,500 molecules of thrombospondin per platelet could bind more than 100,000 molecules of plasma fibronectin per cell following thrombin stimulation. Paper-4472414.
Recombinant pieces of TSP-1 and TSP-2 incorporating combinations of domains that span the entire subunit were produced in insect cells and examined for VWF reductase activity. Paper-9574251.
Although high TSP-1 expression was associated with good prognosis in patients with low VEGF-expressing tumors, TSP-1 itself appeared to have no overall impact on survival. Paper-1883553.
BACKGROUND: Thrombospondin-1 ( TSP-1) promotes breast cancer cell invasion of collagen by upregulating matrix metalloproteinase-9 ( MMP-9) production. Paper-9549213.
These changes could directly contribute to the loss or weakened binding between TSP1 and CRT and the resultant effects on TSP1- CRT binding-induced cellular activities. Paper-15639483.
TSP-1 is predominantly a negative regulator of DC and T cell function while basal SIRP-alpha ligation on APC by CD47 enforces tolerance. Paper-13034706.
Decorin inhibits cell attachment to thrombospondin-1 by binding to a KKTR-dependent cell adhesive site present within the N-terminal domain of thrombospondin-1. Paper-1212008.
These studies suggest that CD36 is involved in regulation of resorption by osteoclasts and is the receptor responsible for the resorption- promoting effects of TSP-1. Paper-8491742.
Thrombospondin-1 suppresses spontaneous tumor growth and inhibits activation of matrix metalloproteinase-9 and mobilization of vascular endothelial growth factor. Paper-9078772.
Here, we report that TFPI binds specifically and saturably to thrombospondin-1 ( TSP-1) purified from platelet alpha-granules with an apparent K(D) of approximately 7.5 nm. Paper-8628530.
CD47-expressing cells preferentially bind to other CD47-expressing cells, and intercellular adhesion requires stimulation by serum or a CD47- binding peptide from TSP. Paper-10781342.
Finally, we established that the TSP-1- stimulated FTC cell invasion is wholly abolished under anti- uPA blocking antibodies or aprotinin treatments whereas MMP inhibitors have no effect. Paper-12842915.
Thrombospondin was cleaved by neutrophil elastase, but the site(s) of the limited cleavage are independent of the competitive inhibition of elastase activity by thrombospondin. Paper-7780803.
Also, increased ID1 was associated with loss of thrombospondin-1 ( TSP-1) expression, a known inhibitor of angiogenesis, and increased intensity of ephrin-A1 and its receptor EPHA2. Paper-11000234.
The ability of TSP to convert latent TGF-beta to biologically active TGF-beta suggests that TSP is a major regulatory factor in the control of TGF-beta activity. Paper-136507.
The above observations together suggest that U19/ EAF2 regulates the expression of TSP-1 via blocking p53 repression of the TSP-1 promoter. Paper-14214851.
Our in vitro and in vivo data demonstrate that ELL could also serve as a transcriptional factor to directly induce transcription of the thrombospondin-1 ( TSP-1) gene. Paper-13872921.
Furthermore, TSP- associated TGF-beta is biologically active, and the binding of TGF-beta to TSP may protect TGF-beta from extracellular inactivators. Paper-7406156.
These findings suggest that activation of L- TGF-beta1 by plasmin occurs at the cell surface of activated alveolar macrophages and requires a TSP-1/ CD36 interaction. Paper-2000875.
We now show that TSP-dependent platelet-monocyte interactions are mediated by glycoprotein IV ( GPIV), an intrinsic membrane protein recently identified as a cell surface TSP receptor. Paper-6465824.
Purified Lys- Plg (the plasmin modified form of native Glu- Plg) bound to TSP to a greater extent than Glu- Plg, and binding of both forms was augmented by Plg activators. Paper-5411521.
ATF-1 knockdown prevented HGF- induced down-regulation of TSP-1 promoter activity and protein expression and also reduced HGF-dependent tumor cell invasion. Paper-13247361.
TSP1 is an important link between adipocytes and macrophage-driven adipose tissue inflammation and may mediate the elevation of PAI-1 that promotes a prothrombotic state. Paper-12710649.
The N-terminal module of thrombospondin-1 interacts with the link domain of TSG-6 and enhances its covalent association with the heavy chains of inter-alpha-trypsin inhibitor. Paper-10794403.
The number of neural crest cells that remain attached to 4 microg/ml of thrombospondin-1 is similar to the number that remain attached to dishes coated with 10 microg/ml of fibronectin. Paper-1893558.
Thrombospondin-1 ( TSP-1) up-regulates tissue inhibitor of metalloproteinase-1 ( TIMP-1) production in human tumor cells: exploring the functional significance in tumor cell invasion. Paper-14152850.
Blockade of the p38 MAPK pathway by SB203580 remarkably inhibited the phosphorylation of HSP27 induced by 5-FU and decreased the induction of Egr-1 and TSP-1 by 5-FU in KM12C cells. Paper-12922921.
However, the role of TSP-1- TGFbeta1 pathway in the development of glucose- induced imbalance of ECM homeostasis in skin connective tissue is not studied. Paper-10191157.
Monoclonal antibodies to GPIV bound to cells of the human monocytoid line U937 as assessed by flow cytometry and inhibited the binding of 125I- TSP to the cell surface by 83%. Paper-6465824.
CD36- mediated signal transduction in human monocytes by anti-CD36 antibodies but not by anti-thrombospondin antibodies recognizing cell membrane- bound thrombospondin. Paper-7189561.
To determine if an interaction between TS-1 and IGFBP-5 was the primary determinant of the inhibitory effect of IGFBP-5, an IGFBP-5 mutant that bound poorly to TS-1 was utilized. Paper-10766176.
Activating transcription factor-1- mediated hepatocyte growth factor- induced down-regulation of thrombospondin-1 expression leads to thyroid cancer cell invasion. Paper-13247361.
Fibroblasts lacking LRP1 or expressing calreticulin lacking the TSP1 binding site do not respond to TSP1 with anchorage-independent survival. Paper-13065497.
The inclusion of TSP-1 blocking peptide to cells stimulated with elevated glucose concentration abrogated activation of TGF-beta1 and induction of FN secretion. Paper-12110694.
In assays performed in vitro of endothelial cell migration and tube formation, and in vivo corneal angiogenesis assays, HRGP inhibited the antiangiogenic effect of TSP-1. Paper-8689729.
Furthermore, thrombospondin-1 that was secreted in the culture medium was significantly increased (3.8-fold) as compared with that of the viral control 36 h after infection with Ad5CMV- p53. Paper-9875594.
CONCLUSIONS: This study shows that TSP-1 enhances angiogenesis due to its positive correlation with VEGF and MVD, and is a good prognostic factor for survival in advanced gastric cancer. Paper-15793722.
FGF-2- stimulated endothelial cell migration was either further stimulated or inhibited by TSP-1, following the same bi-phasic dose response as in the absence of FGF-2. Paper-12941963.
TSP/hep I signals focal adhesion disassembly by binding cell surface calreticulin ( CRT) and activating phosphoinositide 3-kinase ( PI3K). Paper-9163692.
These data show that the WSXW motif binds VLAL on both LAP and mature TGF-beta, and these interactions are critical for TSP1- mediated activation of the TGF-beta latent complex. Paper-11424677.
Similar to platelet TSP-1, these proteins are potent inhibitors of endothelial cell migration, and 3TSR of human TSP-1 (3TSR/ hTSP-1) and TSR2+RFK activate TGFbeta. Paper-9088178.
It may serve as a receptor for collagen and is also able to bind thrombospondin ( TSP), because a monoclonal antibody to CD36 inhibits TSP binding to thrombin-stimulated platelets. Paper-7601269.
Although MMP2 interacted with TSP1 and TSP2 via its gelatin-binding domain or a closely mapping site, neither TSP1 nor TSP2 was degraded by MMP2 in vitro. Paper-8628587.
Integrin-associated protein ( IAP or CD47) is a receptor for the cell/platelet- binding domain (CBD) of thrombospondin-1 ( TS1), the most abundant protein of platelet alpha granules. Paper-1036118.
Disruption of CD47- TSP-1 interaction by TSP-1- blocking antibodies or down-regulation of CD47 on tumor cells by RNA interference abrogates tumor-induced osteoclast formation. Paper-14051879.
Matrix-bound TSP-1 promotes capillary tube formation in the rat aorta model of angiogenesis, while TSP-1 inhibits bFGF- induced angiogenesis in the rat cornea model. Paper-9055090.
We conclude that TSP-1, in a receptor-mediated process that involves the activation of TGF-beta1, upregulates PAI-1 expression in pancreatic cancer without an effect on uPA production. Paper-8349075.
In the present study, we showed that skin DCN and bone DCN ( chondroitin sulfate-rich proteoglycan) were quantitatively identical with respect to their ability to interact with TSP. Paper-1212008.
We therefore suggest that AKAP12 in astrocytes differentially regulates the expression of VEGF and TSP-1 via the inhibition of PKCzeta phosphorylation and Rho kinase activity in HRMECs. Paper-14309546.
Silencing of CD26 using small interfering RNA or Ab- induced modulation of CD26 also increased TSP-1 expression and enhanced cytoplasmic spreading and T cell migration markedly. Paper-13971856.
A novel interplay between Epac/ Rap1 and mitogen- activated protein kinase kinase 5/extracellular signal- regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis. Paper-14145632.
Most of the active TGF-beta released from platelets after degranulation was associated with TSP, as demonstrated by anti- TSP immunoaffinity and gel permeation chromatography. Paper-7406156.
Human platelet glycoprotein IIIb binds to thrombospondin fragments bearing the C-terminal region, and/or the type I repeats (CSVTCG motif), but not to the N-terminal heparin-binding region. Paper-61743.
Peptides spanning aa 19-36 (RWIESKHKSDFGKFVLSS) blocked hep I-stimulated focal adhesion disassembly, indicating that the TSP/hep I- binding site is located to this sequence in calreticulin. Paper-9171542.
Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/ Rap1 by inducing Id1 and suppressing TSP1 expression. Paper-14145632.
This study defines a TSP1 binding site conserved between LIMPII and CD36 and suggests that cell surface LIMPII may function in some circumstances as an adhesion receptor for TSP1. Paper-1348052.
TGF-beta1- induced thrombospondin-1 expression through the p38 MAPK pathway is abolished by fluvastatin in human coronary artery smooth muscle cells. Paper-11993479.
We evaluated the RNA expression of p53, hdm2, and the p53- targeted p21waf-1 and thrombospondin (tsp)-1 by primary DBC tissues, then correlated the RNA levels with patient clinicopathological data. Paper-14172188.
At the protein level, TGF-beta1 showed a slightly higher expression, and the signal-transducing TGFBR1 and the TGF-beta- activating THBS1 a significantly higher expression in RA SFBs than in OA SFBs. Paper-12559211.
CONCLUSIONS: Our study suggested that TSP1 played competitively inhibitory role in ADAMTS13 binding and cleaving of VWF, and the potential competition might happen within A2 and A3 domains. Paper-15454502.
Using a peptide array approach followed by binding assays with synthetic peptides and recombinant proteins, we identified a FGF-2 binding sequence of TSP-1 in the 15-mer sequence DDDDDNDKIPDDRDN. Paper-14276049.
TSP1- VWF interactions do not strictly enhance platelet recruitment and secreted TSP1 even weakly competes with the dynamic platelet rolling and adhesion onto VWF. Paper-13034704.
These studies therefore identify the alpha4beta1 integrin on SS RBCs as a CD47- activated receptor for TSP, VCAM-1, and plasma fibronectin, revealing novel binding characteristics of this integrin. Paper-10627824.
TSP-1 catabolism is mediated by the low density lipoprotein receptor-related protein ( LRP), a large endocytic receptor that is a member of the low density lipoprotein receptor family. Paper-946032.
In this paper, we report that the expression of an anti-angiogenic protein, thrombospondin-1 ( TSP-1) is down-regulated in the prostate and liver of U19/ EAF2 knockout mouse. Paper-14214851.
Prior EGFR-selective PTK inhibition with AG1478 or ErbB2-selective PTK inhibition with AG825 protected against TSP1-induced tyrosine phosphorylation of ZA proteins and barrier disruption. Paper-16051906.
These data preclude any simple model in which newly surface expressed thrombospondin (or other alpha-granule protein) functions as the major thrombin- stimulated plasma fibronectin receptor in this cell type. Paper-4472414.
Baseline mitogenic activity and activity stimulated by either bFGF or LPA on BAE cells was inhibited by human TSP1 purified from platelets or a recombinant source with a similar dose response. Paper-888052.
Moreover, we show that PRMT6-deficient U2OS cells exhibited cell migration defects that were rescued by blocking the secreted TSP-1 with a neutralizing peptide or blocking alpha- TSP-1 antibody. Paper-14547337.
The TSP- promoted aggregation of nonstimulated platelets was inhibited by a monoclonal antibody to platelet glycoprotein IV ( GPIV), but not by a monoclonal antibody to the fibrinogen receptor, GPIIb-IIIa. Paper-6085252.
Skin decorin ( DCN) is an antiadhesive dermatan sulfate-rich proteoglycan that interacts with thrombospondin-1 ( TSP) and inhibits fibroblast adhesion to TSP [Winnemöller et al., 1992]. Paper-1212008.
To determine the mechanism by which IGFBP-5 binding to TS-1 inhibited cellular responses to TS-1 plus IGF-I, TS-1 binding to integrin associated protein ( IAP) was assessed. Paper-10766176.
The TSP- HRGP- Plg complex bound a similar amount of heparin as the TSP- HRGP complex, demonstrating that the HRGP within the trimolecular complex maintained functional capability. Paper-5079045.
BACKGROUND: CD36 is a suspected facilitator of long chain fatty acid transport and as a thrombospondin ( TSP) receptor, thereby being implicated in cell proliferation, angiogenesis and tumor metastasis. Paper-10688124.
We have previously shown that thrombospondin-1 ( TSP-1) and TGF-beta 1 upregulate the urokinase plasminogen activator ( uPA) and its receptor (uPAR) and promote tumor cell invasion in breast cancer. Paper-1515843.
Taken together, these results strongly suggest that trichostatin A activates the transcription of TSP1 gene through the binding of transcription factor CBF to CCAAT box and the enhanced histone acetylation. Paper-12761944.
Using a neutralizing antibody to transforming growth factor beta ( TGF-beta) or purified TGF-beta1 we further demonstrated that the effects of TSP were not mediated through activation of latent TGF-beta. Paper-1292624.
The inhibitory effect of TSP-1 on cAMP signaling could be reproduced with a peptide possessing a CD36 binding sequence of TSP-1, while the effects of TSP-1 were prevented by a CD36 blocking antibody. Paper-15447526.
Transfection of Bowes melanoma cells with a chimeric LIMPII cDNA that targets expression to the plasma membrane conferred the ability to bind 125I- TSP1 and to adhere to TSP1-coated surfaces. Paper-1348052.
However, in the presence of plasmin both latency-associated peptide and TGF-beta1 were decreased in the same cell lysates, indicating that L- TGF-beta1 associated with TSP-1 is released by plasmin. Paper-2000875.
TSP-1 reduced in vitro tubulogenesis of endothelial cells when grown in conditioned medium from pancreatic cancer cells expressing sst2, as compared to those expressing the control vector. Paper-14059837.
The chemokine-induced expression of TSP-1 and CD91 was mimicked by inhibitors of CD26 and CXCL12 and CCL5 as well as inhibitors of CD26 stimulated polarized cytoplasmic spreading and migration through TSP-1. Paper-13971856.
To study the mechanisms by which HGF down-regulated TSP-1 expression, we transiently transfected a panel of deleted human TSP-1 promoter reporter plasmids into papillary thyroid carcinoma cells. Paper-13247361.
LRP- mediated endocytic clearance of (125)I-pro- MMP-2 was inhibited by anti- TSP antibodies and accelerated upon complexing with TSP-1, but these treatments had no effect on (125)I-pro-MMP-2.TIMP-2 uptake. Paper-10855532.
This study thus investigates the role of TSP-1 in mediating elevated glucose-induction of TGF-beta1 bioactivation and fibronectin ( FN) synthesis in human proximal tubular epithelial cells. Paper-12110694.
Spreading of the cells, but not adhesion, on sparse VN coatings is markedly enhanced by the presence of soluble TS1, the recombinant CBD and 4N1K, but not the "mutant" peptide 4NGG, KRFYGGMWKK, which fails to bind IAP. Paper-739077.
Results showed that mutations of Lys 24 and Lys 32 in TSP1 to Ala and of amino acids 24-26 and 32-34 in CRT to Ala significantly weakened the binding of TSP1 and CRT, which is consistent with experimental results. Paper-15070052.
These findings suggest that the p38 MAPK pathway plays a crucial role in the induction of Egr-1 by 5-FU and that induced Egr-1 augments TSP-1 promoter activity, with the subsequent production of TSP-1 mRNA and protein. Paper-12922921.
HYPOTHESIS: We hypothesized that p53 mutations (mp53) are associated with decreased expression of thrombospondin 1 ( TSP-1) and that decreased TSP-1 expression is associated with lymph node metastases. Paper-13396567.
These findings show that TSP-1 is a transcriptional repression target of PRMT6 and suggest that neutralizing the activity of PRMT6 could inhibit tumor progression and therefore may be of cancer therapeutic significance. Paper-14547337.
TGF-beta blocking antibody or TGF-beta1 antisense oligonucleotide markedly reduced the up-regulated TSP-1 expression in scleroderma fibroblasts but had little effect on normal fibroblasts. Paper-10780050.
Finally, studies using zebrafish confirmed that ELL regulates TSP-1 mRNA expression in vivo, and ELL could inhibit zebrafish vasculogenesis, at least in part, through up-regulating TSP-1. Paper-13872921.
Together, these findings suggest that hypoxic and oncogenic signals could interact in the tumor microenvironment to inhibit TSP-1 and induce VEGF expression, promoting the switch to the angiogenic phenotype. Paper-8627350.
These results indicate that TGFbeta1 treatment may regulate angiogenesis in pituitary cells by initially increasing levels of pro-angiogenic VEGF-A and then stimulating the anti-angiogenic molecules TSP-1 and TSP-2 levels. Paper-10921155.
CONCLUSION: Both inflammation and angiogenesis were decreased after TSP1-derived peptide treatment indicating a potential pathway by which TSP1 interaction with neutrophils induces CTGF in RA affected tissues. Paper-13136655.
These results indicate that TSP-1 binding to LRP-1 does not require prior or concomitant interaction with cell surface HSPG but suggest subsequent endocytosis requires high-affinity heparin-binding. Paper-10501412.
When the cell migration response was assessed, the response to IGF-I plus TS-1 was also significantly inhibited by the addition of IGFBP-5, whereas 1.0 microg/ml of IGFBP-5 alone had no effect on the response to IGF-I. Paper-10766176.
A peptide derived from the C-terminal IAP binding site of TSP also supports sickle cell adhesion; adhesion to this peptide or to TSP is inhibited specifically by the anti- IAP monoclonal antibody, 1F7. Paper-8713002.
Overexpression of various members of the CRE-binding protein family identified activating transcription factor-1 ( ATF-1) as the transcription factor responsible for HGF- induced repression of TSP-1 promoter activity. Paper-13247361.
Elevated glucose induction of thrombospondin-1 up-regulates fibronectin synthesis in proximal renal tubular epithelial cells through TGF-beta1 dependent and TGF-beta1 independent pathways. Paper-12110694.
PRMT6 associates with the TSP-1 promoter and regulates the balance of methylation of H3R2 and H3K4, such that in PRMT6-deficient cells H3R2 was hypomethylated and H3K4 was trimethylated at the TSP-1 promoter. Paper-14547337.
Short peptide fragments derived from the type I properdin repeats of the TSP1 molecule mimic anti-angiogenic and/or transforming growth factor-beta (TGF-beta)- activating properties of the whole TSP1 glycoprotein. Paper-1888586.
In endothelial cells, however, the internalization of TSP1 was not mediated by LRP but since RAP inhibited TSP1 uptake and degradation, we postulate that another member of the LDLR family is likely to be involved. Paper-249770.
To test whether LIMPII also binds TSP1, a LIMPII peptide corresponding to the TSP1 binding domain of CD36 was expressed as a recombinant glutathione S-transferase ( GST) fusion protein. Paper-1348052.
TSP-1 levels remained unchanged but the levels of secreted VEGF in the high grade UMUC-3 and 253J cell lines were significantly decreased 5 to 50-fold and a corresponding decrease in net angiogenic activity was observed. Paper-8839804.
Given that anti- CD47 treatment of platelets did not further decrease the adhesion of anti-CD36-treated platelets and CD36 is a TSP-1 receptor, it appears that CD36/ TSP-1 interaction could trigger the CD47-dependent pathway. Paper-9899266.
Pretreatment of DCs with anti- CD47 blocking Ab or knocking down the expression of CD47 or TSP-1, but not signal regulatory protein alpha by small interfering RNA, abrogated the suppressive effect of E. coli K1. Paper-15343481.
We show that txr1 impedes taxane- induced apoptosis in tumor cells by transcriptionally down-regulating the production of thrombospondin-1 (TSP-1)--known earlier for both its anti-angiogenic and proapoptotic actions. Paper-12161686.
The N-terminal domain of TSP1 binds to the calreticulin- LRP1 receptor co-complex to signal down-regulation of cell adhesion and increased cell motility through focal adhesion disassembly. Paper-13065497.
We have identified a novel missense mutation which substitutes a glycine for an aspartic acid residue in the thrombospondin ( TSP) type 3 calcium- binding domain of COMP in a patient diagnosed with PSACH. Paper-8894503.
Cellular internalization and degradation of thrombospondin-1 is mediated by the amino-terminal heparin binding domain (HBD). High affinity interaction of dimeric HBD with the low density lipoprotein receptor-related protein. Paper-946032.
The serine-proteinase cathepsin G ( CG) is a potent agonist of platelet aggregation inducing the release and surface expression of alpha-granule adhesive proteins such as fibrinogen (Fg) and thrombospondin-1 ( TSP-1). Paper-553064.
The action of TGF-betas very likely requires local activation by thrombospondin-1 and is partly mediated by its downstream mediator connective tissue growth factor, both of which are constitutively expressed in the trabecular meshwork. Paper-13727726.
This is followed by an increase in the expression of the p53- induced thrombospondin (TSP)-1, a VSMC growth and motility factor, and human double minute 2 (HDM2), an antagonist of p53 transcriptional and growth suppressive activity. Paper-15134772.
It is known that HGF/ SF induces in vitro expression of vascular endothelial growth factor ( VEGF), a key agonist of tumor angiogenesis; by contrast, thrombospondin 1 ( TSP-1) is a negative regulator of angiogenesis. Paper-10165189.
Analysis of rodent cells that differ in their p53 genotype (p53+/+ or p53-/-) indicated that in vitro exposure to hypoxia simultaneously suppressed TSP-1 and induced VEGF expression, regardless of the p53 genotype. Paper-8627350.
Our results suggest that platelet TSP-1 released in a wound stimulates endothelial cell tubulogenesis through an upregulation of DF VEGF expression and a downregulation of endothelial cell PAI-1 expression. Paper-12454718.
The majority of the JDM children with the TNF alpha-308A allele (7/12) produced more TSP-1 than their TNF alpha-308G counterparts ( P < 0.05), and their TSP-1 values were inversely related to those for PF4 ( P < 0.0006). Paper-9532514.
A putative progestin-response element was identified in the human TSP-1 promoter, which is consistent with the hypothesis that a progestin- PR complex might directly regulate transcription of the TSP-1 gene in human cells. Paper-13943586.
Interestingly, by screening 96 tumor-related genes, we observed that the expression of Cx26 or GFP- Cx26 in the tumor cells up-regulated both the transcription and the translation of thrombospondin-1 ( TSP-1), an anti-angiogenic molecule. Paper-10177002.
Thrombospondin ( TSP) and transforming growth factor beta 1 ( TGF-beta) promote human A549 lung carcinoma cell plasminogen activator inhibitor type 1 ( PAI-1) production and stimulate tumor cell attachment in vitro. Paper-132528.
In a competitive binding assay, neutrophil elastase bound to thrombospondin with a dissociation constant of 17 +/- 7 nM, expressed per mole of thrombospondin trimer, or 52 +/- 20 nM, expressed per mole of thrombospondin subunit. Paper-7780803.
TSP was extremely sensitive to degradation by all enzymes except thrombin, whereas vWF released from the ECM was more resistant to proteolysis than constitutively secreted vWF, and FN was poorly degraded by plasmin. Paper-8352736.
Adhesion via integrins to ICAM-1 or ECM components up-regulates TSP turnover dramatically from a low level in nonadherent cells, whereas CD3 stimulation inhibits TSP turnover through interference with CD91/ CRT-mediated internalization. Paper-12281880.
Thrombospondin 1 is a tight- binding competitive inhibitor of neutrophil cathepsin G. Determination of the kinetic mechanism of inhibition and localization of cathepsin G binding to the thrombospondin 1 type 3 repeats. Paper-102069.
BACKGROUND AND AIMS: Thrombospondin 1 ( TSP-1) is an important activator of latent transforming growth factor beta ( TGF-beta) but little is known of the expression patterns and functions of TSP-1 in liver cells. Paper-11181221.
Incubation of purified TSP-1 with vWF resulted in formation of thiol-dependent complexes of TSP-1 and vWF, generation of new thiols in vWF, and reduction in the average multimer size of vWF. Paper-8993305.
The ability of TSP1 to inhibit MMP3-dependent activation of pro- MMP9 and thrombin- induced activation of pro- MMP2 suggests that the TSPs may inhibit MMP activity by preventing activation of the MMP2 and MMP9 zymogens. Paper-8628587.
RESULTS: TIGR/ MYOC colocalized with fibronectin, laminin, and type IV collagen, but not thrombospondin in both dexamethasone and dexamethasone/ascorbate-treated HTM cultures and in TM-1 cultures transfected with TIGR/ MYOC cDNA. Paper-9351167.
These TSP-1 motifs also compete with the fibronectin Hep II domain for binding to syndecan-4 on endothelial cell surface, indicating that they may exert their effects by interfering with the recognition of fibronectin by syndecan-4. Paper-12671605.
In addition to its interaction with vWF, we show that OPG also binds with high avidity to the vWF reductase, thrombospondin ( TSP-1), raising the intriguing possibility that OPG may provide a link between TSP-1 and vWF. Paper-10732848.
Thrombospondin-1 ( TSP1) binding to calreticulin ( CRT) on the cell surface signals focal adhesion disassembly, leading to the intermediate adhesive phenotype, cell migration, anoikis resistance, and collagen stimulation. Paper-15639483.
In a TSP-1 promoter-driven luciferase reporter assay, p53 transfection suppressed the TSP-1 promoter activity and U19/ EAF2 co-transfection blocked the p53 suppression of TSP-1 promoter. Paper-14214851.
SF binding was modulated by binding interactions among ECM molecules ( TSP-1- Fn, TSP-1-collagen I, and Fn-collagen I), suggesting that the matrix capacity to bind SF depends upon its exact composition. Paper-664762.
Thrombospondin-1 ( TSP1) binding to calreticulin ( CRT) on the cell surface stimulates association of CRT with LDL receptor-related protein ( LRP1) to signal focal adhesion disassembly and engagement of cellular activities. Paper-15070052.
The central role played by TSP1 in the control of matrix-degrading enzyme activation and catabolism reveals attractive tracks of research and highlights the involvement of the lipoprotein receptor-related protein ( LRP) receptor in these events. Paper-10541029.
In addition, heparan sulfate drastically inhibited [125I]DCN binding to solid-phase adsorbed TSP (80% inhibition), suggesting that DCN could bind to the N-terminal domain of TSP through interaction with heparin-binding sequences. Paper-1212008.
We conclude that fluvastatin decreases expression of TSP-1 and abolishes the ability of TGF-beta1 to induce TSP-1 expression in HCASMC; this may be achieved by preventing signalling through the p38 MAPK pathway. Paper-11993479.
TSP- induced proliferation was inhibited by antibodies that block TSP binding to IAP and mimicked by 4N1K, a 10-amino acid peptide derived from the IAP binding site within the carboxyl terminus of TSP. Paper-8874937.
Mesangial cell upregulation of TSP-1 is associated with migration and proliferation but not maximal ECM accumulation, whereas mesangial cell expression of Fn-EIIIA is associated with proliferation and ECM accumulation. Paper-1804233.
In the cause of studying the effects of thrombospondin on other serine proteinases, we found that thrombospondin binds neutrophil elastase in an active-site-dependent manner and competitively inhibits the activity of the enzyme. Paper-7780803.
Therefore, the fatty acid translocase activity of CD36 elicits proangiogenic signaling in vascular cells, and TSP1 inhibits this response by simultaneously inhibiting fatty acid uptake via CD36 and downstream cGMP signaling via CD47. Paper-13239049.
Here we examine the effects of the TS1 CBD and 4N1K (KRFYVVMWKK), a cell-binding peptide derived from it, on the adhesion and spreading on vitronectin ( VN) of C32 human melanoma cells which express IAP, alpha v beta 3, and alpha v beta 5. Paper-739077.
Furthermore, tumour cell thrombospondin-1 promoted tumour cell invasion and decreased tumour cell adhesion through up-regulation of urokinase plasminogen activator receptor-controlled urokinase plasminogen activator and plasmin activities. Paper-8397710.
While neither ligand inhibited complex formation of the other with TSP, 10 mM epsilon-amino-n-caproic acid selectively blocked incorporation of Plg into the complex, suggesting that TSP contains independent binding sites for Plg and HRGP. Paper-5079045.
Thrombospondin ( TSP) is a multifunctional platelet alpha-granule and extracellular matrix glycoprotein that binds specifically to plasminogen ( Plg) via that protein's lysine-binding site and modulates activation by tissue activator (TPA). Paper-5411521.
These results indicate that CD26 is an endogenous inhibitor of T cell motility through inhibition of TSP-1 expression and that chemokines stimulate cell polarity and migration through abrogation of the CD26-dependent inhibition. Paper-13971856.
This TSP1 peptide-dependent activation of AP-1 was inhibited by both heparin and the MAP/ ERK kinase inhibitor PD98059, providing a functional link between adhesion molecule interaction and nuclear transactivation events via the MAP kinase pathways. Paper-2020313.
Further, we have shown that recombinant TSP-1 is able to block proliferation and induce apoptosis at concentrations consistent with those found in the plasma of patients with SSc and that its effect occurs in the presence of elevated VEGF levels. Paper-16059686.
Our results identify syndecan-4 as a novel receptor for the N-terminus of TSP-1 and suggest that TSP-1 N-terminal pro-angiogenic activity is linked to its capacity of interfering with syndecan-4 functions in the course of cell adhesion. Paper-12671605.
Because TSP-1 but not TGF-beta1 is a natural ligand for CD36, these findings suggest that the L- TGF-beta1 in a complex with TSP-1 localizes to the macrophage cell surface when TSP-1 interacts with its receptor, CD36. Paper-2000875.
CONCLUSIONS: TGF-beta 2 is capable of inducing the expression of ECM and basement membrane components in cultured ONH astrocytes via CTGF and upregulated TSP-1, a protein naturally involved in the activation of latent TGF-beta. Paper-11200622.
Thrombin induces saturable platelet binding sites for plasma fibronectin and concurrently stimulates surface expression of a number of platelet alpha-granule constituents including thrombospondin and fibrin which are known to interact with fibronectin. Paper-4472414.
Neutrophil elastase inactivated with phenylmethylsulfonyl fluoride did not compete with active elastase for binding to thrombospondin, implying that a functional active site is important for the interaction of elastase with thrombospondin. Paper-7780803.
The WSXW sequences in the type 1 repeats of TSP1 interact with the mature domain of TGF-beta, and WSXW peptides inhibit TSP1- mediated activation by blocking TSP1 binding to the TGF-beta latent complex. Paper-11424677.
In vitro, TSP1 acutely induces expression of plasminogen activator inhibitor-1 ( PAI-1) by monocytic cells, suggesting that TSP1- induced macrophage recruitment is at least partially mediated by PAI-1. Paper-12922928.
In this study, we demonstrate that infection of DCs with OmpA(+) E. coli significantly upregulates the expression of CD47, an integrin-associated protein, and its natural ligand thrombospondin 1 ( TSP-1). Paper-15343481.
We conclude that the increased circulating concentrations of TSP-1 associated with the TNF alpha-308A allele suggest that this anti-angiogenic regulator may play a significant role in the augmented vascular occlusion observed in JDM children with this genetic marker. Paper-9532514.
A recent study reveals that cyclin D1 acts to promote cell migration by inhibiting Rho/ROCK signaling and expression of thrombospondin-1 ( TSP-1), an extracellular matrix protein that regulates cell migration in many settings including cancer. Paper-14722087.
Taken together, these data provide compelling evidence that the amino-terminal domain of TSP-1 binds to LRP and thus the recognition determinants on TSP-1 for both LRP and for cell surface proteoglycans reside within the same TSP-1 domain. Paper-946032.
In addition, when released from thrombin-stimulated platelets, thrombospondin and osteonectin bound to anti- thrombospondin IgG-coated plates indicating that osteonectin was complexed to thrombospondin once the platelet-release reaction has occurred. Paper-6097048.
Tumour cell thrombospondin-1 induced a 2-7 fold increase in urokinase plasminogen activator receptor and cell-associated urokinase plasminogen activator expression and a 50-65% increase in cell-associated urokinase plasminogen activator and plasmin activities. Paper-8397710.
In the presence of 2 mM calcium ions, 2.9 +/- 0.4 mol of cathepsin G interacted with 1 mol of thrombospondin 1 trimer with a site-binding constant of 7.0 +/- 3.5 nM, which reduced the efficiency of hydrolysis of Suc-Ala-Ala-Pro-Phe-p-nitroanilide 8.5 +/- 1.4-fold. Paper-102069.
In order to better understand TSP- mediated activation of cell- secreted latent TGF-beta, we examined the consequences of interactions of the large (platelet-derived) and small (recombinant) forms of latent TGF-beta with TSP in a chemically defined system. Paper-136507.
Using an enzyme-linked immunosorbent assay and a TSP-Sepharose affinity bead-binding assay we have found that Plg- TSP complex formation was markedly enhanced (up to 5-fold) when catalytic concentrations of Plg activators were included in the reaction mixtures. Paper-5411521.
EGF induced activation of TSP-1 promoter-driven luciferase activity in HuH-7 cells, and the elements between -267 and -71 on the 5' region of TSP-1 gene containing two GC boxes to which Sp1 bound, were found to be responsible for the promoter activation by EGF. Paper-9432656.
We show that one peptide CSVTCG, which represents the CD36- binding region of TSP-1, stimulates resorption in a fashion similar to the intact molecule, while the peptides RGDS, RFYVVMWK, and RFYVVM, representing other cell-binding domains of TSP, have no effect on resorption. Paper-8491742.
Low concentrations of soluble TSP prime for both N-formyl-methionyl-leucyl-phenylalanine (FMLP)-mediated O2- generation and chemotaxis, whereas VN suppresses FMLP-mediated O2- generation but primes for FMLP-mediated chemotaxis. Paper-7851231.
The extracellular matrix ( ECM) glycoprotein thrombospondin-1 ( TSP-1) has been reported to activate the latent complex of transforming growth factor-beta ( TGF-beta), the major effects of which in mesenchymal cells is stimulation of the synthesis of ECM. Paper-10780050.
TSP1 enhances covalent modification of the inter-alpha-trypsin inhibitor by TSG-6 and transfer of its heavy chains to hyaluronan, suggesting a physiological function of TSP1 binding to TSG-6 in regulation of hyaluronan metabolism at sites of inflammation. Paper-10794403.
A 16-residue synthetic peptide, which represents the amino acids linking kringle 4 to kringle 5 (residues 435-450 of native plasminogen), was without effect in either binding to thrombospondin or blocking the binding of thrombospondin to plasminogen. Paper-6459159.
Endogenous calreticulin binding to the N-terminal domain of endogenous thrombospondin-1 elicited a motogenic signal to the T cells through the C-terminal domain of thrombospondin-1 and its cell surface receptor integrin-associated protein (CD47). Paper-10780464.
Thrombospondin ( TSP) induces reorganization of the actin cytoskeleton and restructuring of focal adhesions through binding of amino acids (aa) 17-35 (hep I peptide) of thrombospondin to a cell surface form of calreticulin ( CRT). Paper-9171542.
G protein signals and ERK phosphorylation are induced by TSP binding to cell surface CRT, because CRT null mouse embryonic fibroblasts (MEF) fail to stimulate ERK phosphorylation in response to TSP/hep I treatment. Paper-9163692.
RESULTS: Skin expression of the TGFbeta- regulated genes cartilage oligomeric matrix protein ( COMP) and thrombospondin 1 ( TSP-1) correlated moderately well with the MRSS, but the addition of other TGFbeta-regulated genes failed to significantly improve best-fit models. Paper-14249002.
Binding of SF to matrices from all three cell lines was significantly inhibited by preincubation of the matrices with antibodies against TSP-1, whereas antibodies against several other ECM components were less effective or ineffective in inhibiting SF binding. Paper-664762.
The abundance of TGF-beta, in conjunction with an augmented mRNA and/or protein expression of TGF-beta- releasing THBS1 and TGFBR1, suggests a pathogenetic role of TGF-beta-induced effects on SFBs in RA, for example, the augmentation of MMP-mediated matrix degradation/remodeling. Paper-12559211.
METHODS: We describe the construction of a CRAd with cancer specific gene transcriptional control using the CXCR4 gene promoter ( TSP) and cancer specific mRNA translational control using a 5'-untranslated region (5'-UTR) element from the FGF-2 ( Fibroblast Growth Factor-2) mRNA. Paper-12741725.
Since it has been reported that HGF can downregulate the expression of TSP-1 mRNA, TSP-1 mRNA levels were measured in 7 primary cultures, established from thyroid papillary carcinomas (TPC), and in 1 TPC cell line prior to, or after, stimulation with HGF. Paper-11545323.
The signals from TSP1 and its derived peptides differentially synergized with activation of the TCR to induce phosphorylation of linker for activation of T cells (LAT) and extracellular signal-regulated kinase (ERK) 1/2, c-Jun N-terminal kinase, and p38 kinases. Paper-2020313.
This rt- TSP1- induced increase in PAI-1 was neutralized by monoclonal antibodies to both TSP and TGF beta. rt- TSP1 also inhibits the proliferation of endothelial cells and this response is also neutralized by TSP and TGF beta antibodies. Paper-7862747.
The secretion of TSP-1 by low- and high-grade cancer cells was reduced >94% when compared to NU cells, and this loss of inhibitory TSP-1 accounted for the development of an angiogenic phenotype because both NU cells and cancer cells secreted similar levels of total stimulatory activity and VEGF. Paper-1360008.
125I- TGF-beta binds to purified TSP in an interaction that is specific in the sense that bound TGF-beta could be displaced by TGF-depleted TSP but not significantly by native TSP, heparin, decorin, alpha 2-macroglobulin, fibronectin, or albumin. Paper-7406156.
Purified platelet thrombospondin binds to fibronectin and fibrinogen immobilized on plastic surfaces with dissociation constants of 1.12 +/- 0.37 X 10(-7) M and 1.27 +/- 0.41 X 10(-7) M respectively, and to thrombospondin immobilized on plastic with dissociation constant of 4.82 +/- 1.01 X 10(-7) M. Paper-4809099.
We investigated CD36 expression and the effect of TSP-1 on megakaryocytopoiesis, with and without pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), and with and without blocking TSP-1 binding with receptor CD36 on megakaryocytic cells. Paper-10014349.
However, this delay in MDA-MB-231/B02 tumor growth upon exposure to TSP-1 was associated with an increased vascular endothelial growth factor ( VEGF) expression in tumor cells themselves, leading to a tumor growth rate comparable to that of tumors whose fibroblasts did not overproduce TSP-1. Paper-11262057.
The amino-terminal domain of the extracellular matrix ( ECM) protein thrombospondin-1 ( TSP-1) mediates binding to cell surface heparan sulfate proteoglycans ( HSPG) as well as binding to the endocytic receptor, low density lipoprotein-related protein ( LRP-1). Paper-10501412.
We studied the binding thermodynamics of the TSP1- CRT complex and the conformational changes in CRT induced by binding to TSP1 with combined binding free energy analysis, molecular dynamics simulation, and anisotropic network model restrained molecular dynamics simulation. Paper-15070052.
This mutant was equipotent compared to native IGFBP-5 in its ability to inhibit both protein synthesis and cell migration responses to IGF-I plus TS-1 thus excluding the possibility that IGFBP-5 was inhibiting the response to TS-1 and IGF-I by inhibiting IGF-I binding to the IGF-I receptor. Paper-10766176.
The inhibitory activity of TSP1 in large vessel and microvascular endothelial cells was replicated by a recombinant domain of the protein containing its CD47- binding site and by a CD47- binding peptide derived from this domain but not by the CD36- binding domain of TSP1. Paper-15535539.
These results indicate that IGFBP-5 inhibits the binding of TS-1 to IAP, and this results in an alteration of the ability of TS-1 to modulate the disruption of the IAP/SHPS-1 interaction which leads to attenuation of the ability of TS-1 to enhance cellular responsiveness to IGF-I. Paper-10766176.
The lymphocyte chemoattractant SDF-1alpha stimulates migration of Jurkat cells through this monolayer only if both the lymphocytes and fibroblasts express CD47, and the inhibition of migration by a CD47- interacting peptide from TSP similarly requires CD47 expression on both cell types. Paper-10781342.
These studies show that activation of latent TGF-beta is mediated by two sequences present in the type 1 repeats of TSP1, a sequence (GGWSHW) that binds active TGF-beta and potentially orients the TSP molecule and a second sequence (RFK) that activates latent TGF-beta. Paper-195312.
In contrast, pertussis toxin specifically blocks only the TS1 stimulated spreading on low density VN, indicating that IAP exerts its effects on signal transduction via a heterotrimeric Gi protein acting upstream of a common cell spreading pathway which includes PI-3 kinase, PKC, and tyrosine kinases. Paper-739077.
Upon validation of the calculated binding affinity changes of the TSP1- CRT complex by mutations in key residues in TSP1 and CRT with the experimental results, we performed conformational analyses to understand the role of TSP1 binding to CRT in the induction of conformational changes in CRT. Paper-15070052.
These data provide evidence that TSP not only has the capacity of functioning as a matrix protein to directly promote cell-substratum adhesion but that TSP can also stimulate cell adhesion and spreading by modulating cell surface protease expression through stimulation of tumor- associated production of PAI-1. Paper-132528.
Thus, the initial production of small amounts of plasmin from Plg immobilized on TSP in fibrin-free microenvironments could generate a positive feedback loop by enzymatically modifying both TSP and Plg, resulting in an increase in TSP- Plg complex formation leading to the localized production of substantially more plasmin. Paper-5411521.
In the presence of EDTA, 5.3 +/- 0.5 mol of cathepsin G interacted with 1 mol of thrombospondin 1 with a site-binding constant of 2.1 +/- 1.6 nM, implying the existence of two binding sites for cathepsin G on each subunit of thrombospondin 1, one or both of which is variably exposed and sensitive to calcium ions. Paper-102069.
These findings suggest that apoptotic fibroblasts release TSP1 as a signal to recruit macrophages while the up-regulated expression of the CD36/ TSP1 complex on their cell surface may form a ligand bridging the fibroblast to a complex consisting of alpha v beta 3/ CD36/ TSP1 on macrophages. Paper-9873948.
Significant amounts of plasmin were generated from the TSP- HRGP- Plg complex (equivalent to that from the TSP- Plg complex), but the rate of plasmin generation from the trimolecular complex was greater than from the bimolecular complex, suggesting an important interaction of HRGP with Plg when both are complexed to TSP. Paper-5079045.
A mutant fusion protein lacking aa 19-36 ( glutathione S-transferase-CRTDeltahep I) failed to restore responsiveness to hep I in crt(-/-) cells, bind thrombospondin, or competitively block focal adhesion disassembly, providing evidence for the role of this calreticulin sequence in mediating thrombospondin signaling. Paper-9171542.
Conformational analyses showed that TSP1 binding to CRT resulted in a more "open" conformation and a significant rotational change for the CRT N-domain with respect to the CRT P-domain, which could expose the potential binding site(s) in CRT for binding to LRP1 to signal focal adhesion disassembly. Paper-15070052.
Given the frequent overexpression of cyclin D1 in cancer cells, due to its upregulation by Ras, Rho, Src, and other genes that drive malignant development, the new findings suggest that cyclin D1 may have a central role in mediating invasion and metastasis of cancer cells by controlling Rho/ROCK signaling and matrix deposition of TSP-1. Paper-14722087.
We have shown previously that thrombospondin 1 ( TSP1), a platelet alpha-granule and extracellular matrix protein, activates latent TGF-beta via a protease- and cell-independent mechanism and have localized the TGF-beta binding/activation region to the type 1 repeats of platelet TSP1. Paper-195312.
Thrombospondin ( TSP) was demonstrated to inhibit the growth of bovine aortic endothelial cells, an activity that was not neutralized by antibodies to TSP or by other agents that block TSP-cell interactions but that partially was reversed by a neutralizing antibody to transforming growth factor-beta ( TGF-beta). Paper-7406156.
The redistribution of platelet membrane glycoprotein IV ( GPIV) and the release of intracellular alpha-granule thrombospondin ( TSP) were examined and the inhibition of beta-thromboglobulin (beta-TG) and platelet factor 4 ( PF4) in patients with chronic myelogenous leukemia (CML) was observed and quantitation of beta-TG and PF4 in sera was conducted. Paper-1484648.
We show in this study that the thrombospondin-1 binding site of calreticulin, spanning aa 19-32, is a major triggering factor for T cell motility and migration within a three-dimensional collagen type 1 matrix, and that exogenous motogenic factors such as chemokines can stimulate migration via a calreticulin- thrombospondin-1 pathway. Paper-10780464.
Taken together, our results indicate that HGF- induced down-regulation of TSP-1 expression is mediated by the interaction of ATF-1 with the CRE binding site in the TSP-1 promoter and that this transcription factor plays a crucial role for tumor invasiveness in papillary carcinoma of the thyroid triggered by HGF. Paper-13247361.
Because activation of latent TGF-beta is a major means of regulating TGF-beta, we addressed the role of TSP1- mediated TGF-beta activation in the development of diabetic cardiomyopathy exacerbated by abdominal aortic coarctation in a rat model of type 1 diabetes using a peptide antagonist of TSP1-dependent TGF-beta activation. Paper-13408117.
This study evaluated the hypothesis that the HMG-CoA reductase inhibitor fluvastatin inhibits TGF-beta1 induced TSP-1 expression via inhibition of p38 mitogen activated protein kinase ( MAPK) phosphorylation in human coronary artery smooth muscle cells (HCASMC) and may therefore have anti-restenosis potential. Paper-11993479.
These synonyms are used for gene THBS1 (thrombospondin 1): TSP-1, TSP1, TSP, Thrombospondin-1, THBS-1, THBS.
These accession numbers are used for gene THBS1: Q15667 (UNIPROT__AC), M14326 (NCBI_GENBANK__AC), AB209912 (NCBI_GENBANK__AC), A8K6H4 (UNIPROT__AC).
THBS1 is a homologue of THBS1 (thrombospondin 1) from Pan troglodytes.
THBS1 is a homologue of THBS1 (thrombospondin 1) from Canis lupus familiaris.
THBS1 is a homologue of THBS1 (thrombospondin 1) from Bos taurus.
THBS1 is a homologue of THBS1 (thrombospondin 1) from Gallus gallus.
THBS1 is a homologue of Thbs1 (thrombospondin 1) from Mus musculus.
THBS1 is a homologue of thbs1 (thrombospondin 1) from Danio rerio.
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