New Anti-Metastatic and Anti-Angiogenic Compound for Ovarian Cancer

摘要

We are studying anastellin, a novel anti-angiogenic protein. We have made significant progress toward understanding the mechanism of action of anastellin, and of polymeric fibronectin, the formation of which is induced by anastellin. We have shown that anastellin is ineffective in mice lacking plasma fibronectin, whereas the activity of the anti-angiogenic form of antithrombin does not depend on plasma fibronectin. As antithrombin is known to bind to another plasma adhesion protein, vitronectin, we also tested anastellin and antithrombin in vitronectin null mice. Antithrombin is inactive in these mice, whereas anastellin is active. Strikingly, a third anti-angiogenic protein, endostatin, was poorly active both in the plasma fibronectin-deficient and vitronectin null mice (Yi et al., PNAS, in press). These results provide strong evidence for our original hypothesis, which predicted that the various anti- angiogenic compounds depend on adhesion proteins, such as fibronectin and vitronectin, for their activity. Drawing from this new understanding of the mechanism of action, we are currently designing anastellin variants with enhanced activities and studying the effects of anastellin on endothelial cells in vitro. These advances in mechanistic understanding will help in designing experimental anti-angiogenic treatments for ovarian cancer.