Thrombospondins and tumor angiogenesis.
The thrombospondins (TSPs) are a family of five secreted proteins that are widely distributed in the extracellular matrix of numerous tissues. TSPs are multimodular and each domain specifies a distinct biological function through interaction with a specific receptor. TSP1 and TSP2 have anti-angiogenic activity, which, at least for TSP1, involves interaction with the microvascular endothelial cell receptor CD36. Expression of TSP1 and TSP2 is modulated by hypoxia and by oncogenes. In several tumors (thyroid, colon, bladder carcinomas), TSP1 expression is inversely correlated with tumor grade and survival rate, whereas in others (e.g. breast carcinomas), it is correlated with the stromal response and is of little prognostic value. Recent studies suggest that TSPs or TSP-derived peptides retaining biological activity could be developed into promising new therapeutic strategies for the anti-angiogenic treatment of solid tumors.
de Fraipont
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INSERM EMI 0105, Dept of Molecular and Structural Biology, Commissariat à l'Energie Atomique, Grenoble, France.
Nicholson
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AC
Feige
J J
JJ
Van Meir
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EG
D000818:Animals; D018955:CD36 Antigens / Q000378:metabolism; D002986:Clinical Trials as Topic; D004268:DNA-Binding Proteins; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009389:Neovascularization, Pathologic; D009857:Oncogenes / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D019699:Thrombospondins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors; D000099262:Thrombospondin 2
D018955:CD36 Antigens; D004268:DNA-Binding Proteins; D029701:Saccharomyces cerevisiae Proteins; D019699:Thrombospondins; D014157:Transcription Factors; D000099262:Thrombospondin 2; C101206:SUB1 protein, S cerevisiae