Angiostatin 4.5

For tumors to grow and metastasize, they must induce the generation of new blood vessels, a process referred to as angiogenesis. Angiogenesis begins when a fibrin clot forms on the external surface of an existing blood vessel, followed by growing of new capillaries. The initial phase begins with increased vascular permeability and local degradation of the vessel wall. The endothelial cells enter the tumor stroma, migrate toward a stimulus such as VEGF or FGF, and proliferate behind the leading edge. At this time, the cells may be most vulnerable to agents that interfere with their proliferation, since they lack protection from other cell types. The next step in vessel formation is recruitment of pericytes, followed by smooth muscle cells. Inhibition of angiogenesis thus provides an important new therapeutic target. The angiogenesis inhibitor angiostatin is a kringle-containing internal fragment of plasminogen, which inhibits cancer growth in numerous animal models …