Mechanisms of thrombospondin-1-mediated metastasis and angiogenesis.

The major route of tumor spread is through the bloodstream. Once in circulation, the tumor cells aggregate in clumps with platelets, which enhances the tumor cell survival. The tumor emboli will then adhere to the endothelium and by the release of proteases extravasation of the cells will occur. One of the platelet-secreted proteins is thrombospondin-1. In this article, thrombospondin-1 will be described as a modulator of angiogenesis through its role in regulating endothelial cell apoptosis, protease expression, and vascular endothelial growth factor expression. We hope to convey the idea that activity of thrombospondin-1 in tumor progression is dependent upon its interaction with several host- and tumor-associated proteins.