Mechanism for the inhibition of angiogenesis by endostatin

In this study we sought to demonstrate the effect of endostatin on endothelial cell adhesion, proliferation, survival and migration in the presence of various ECM proteins. We found that endostatin was able to decrease VEGF-induced adhesion of endothelial cells to a variety of matrices including laminin, collagen IV, fibronectin, collagen I, tenascin-c and vitronectin. Endostatin was also able to inhibit the proliferation of endothelial cells however, this function was more dependent on the ECM proteins upon which the endothelial cells were cultured with the strongest inhibitory effects noted following growth on plastic and the weakest inhibitory effects observed following growth on collagen I or tenascin C which are both tumor associated ECM proteins. We also showed that endostatin did not induce apoptosis of VEGF-treated endothelial cells and in parallel showed that endostatin did not reduce the VEGF-induced activation of the survival protein Akt. (Abstract shortened by UMI.)