How Does Endostatin Inhibit Angiogenesis?
Initial Award Abstract It is now known that the growth and spread of solid tumor cancers, such as breast cancer, absolutely depends on the development of a tumor-associated vasculature by a process known as angiogenesis. Thus, there is considerable interest in finding ways to inhibit angiogenesis as an effective means for preventing tumor progression and metastasis. Our interest is an angiogenesis inhibitor protein called endostatin. It is a proteolytic cleavage product of type XVIII collagen and is one of the most potent angiogenesis inhibitors. Two important findings have increased our interest in endostatin. First, endostatin has been found to inhibit the subcutaneous growth of several tumor types in a mouse model, demonstrating that endostatin works on a wide spectrum of cancers. Secondly, repeated cycles of endostatin treatment have been shown to induce tumor dormancy, suggesting that endostatin treatment does not generate drug resistance. But, the molecular mechanism of endostati
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