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 ar e multimodular and each domain specifies a distinct biological function thr ough interaction with a specific receptor. TSP1 and TSP2 have anti-angiogen ic activity, which, at least for TSP1, involves interaction with the microv ascular endothelial cell receptor CD36. Expression of TSP1 and TSP2 is modu lated by hypoxia and by oncogenes. In several tumors (thyroid, colon, bladd er carcinomas), TSP1 expression is inversely correlated with tumor grade an d survival rate, whereas in others (e.g. breast carcinomas), it is correlat ed with the stromal response and is of little prognostic value. Recent stud ies 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.