Role of Angiogenesis in the Etiology and Prevention of Ovarian Cancer. Project 1: Effect of Angiogenesis Inhibitors in Preventing Ovarian Cancer Growth.

摘要

Primary growth of ovarian cancer and its spreading in the peritoneal cavity as micrometastases are dependent on angiogenesis. Therefore, angiogenesis inhibitors can be used in the prevention and treatment of ovarian cancers. One of the objectives of Project I is the development of a genetically reengineered angiostatic protein, endostatin. During expression cloning of human endostatin, a single point mutation was identified. Mutation lead to the substitution of Proline 125 to an Alanine residue Mutant endostatin (Pl2SA) was expressed in soluble form in large quantities to evaluate its effect against ovarian cancer growth. Native human endostatin was used in parallel studies to determine relative efficacy. Pl2SA endostatin was more potent than native endostatin in inhibiting endothelial cell proliferation and migration in vitro. Mutant endostatin also bound endothelial cells better than the native protein. Furthermore, mutant endostatin inhibited ovarian cancer growth in athymic mice more effectively when compared to native endostatin.