Suppression of tumor growth and metastasis via apoptosis induced specifically in endothelial cells by caspin/PEDF/EPC-1

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We investigated the physiological and pathophysiological roles of caspin/PEDF/EPC-1 in tumor growth and metastasis as an inhibitor of angiogenesis. Supplement of recombinant caspin in the cultures evidently inhibited ex vivo outgrowth of microvessels from excised rat aorta and in vitro growth of cultured endothelial cells in a dose-dependent manner. Furthermore, we found that caspin can induce apoptosis specifically in endothelial cells, but not in any other type of cultured cells. These findings suggest that caspin/PEDF/EPC-1 regulates angiogenesis by inducing apoptosis of endothelial cells. Thus, this protein might play a crucial role in important biological events, in which tissue reconstruction with prominent angiogenesis is essentially required, such as embryogenesis, wound healing, and the formation of granulation tissue as well as tumor growth and metastasis.