It has been shown that tumors, in order to grow and metastasize, must have access to a blood supply. Angiogenesis, or the growth of new blood vessels from existing ones, is the process by which tumor vasculature is formed. Traditional treatments of tumors, such as chemotherapy and radiation, create toxicity and drug resistance which preclude their long term use. A more effective strategy might be to target the growth of blood vessels to inhibit tumor growth rather than targeting the tumor cells themselves. Angiostatin, a fragment of plasminogen, has been shown to be a potent inhibitor of tumor growth and neovasculature in mice and additionally has shown no evidence of drug resistance or toxicity. Its mechanism of action, however, is not well understood. It is likely that angiostatin functions through receptor-mediated signaling but no receptor has yet been identified. This work will isolate the angiostatin receptor as well as potential angiostatin cofactors and characterize signaling molecules in its transduction pathway using traditional biochemical techniques. An understanding of the method by which angiostatin inhibits endothelial cell growth will aid in the design of other angiogenesis inhibitors.
