| Co-Investigator(Kenkyū-buntansha) |
ISHIGURO Naoki Nagoya University, School of Medicine, Lecturer, 大学院・医学部, 講師 (20212871)
KAZAKI Ken-ichi Aichi Medical University, School of Medicine, Lecturer, 医学部, 助手 (50270715)
YOSHIKAWA Kazuhiro Aichi Medical University, School of Medicine, Lecturer, 医学部, 講師 (60109759)
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| Research Abstract |
We investigated the physiological and pathophysiological roles of caspin/PEDF/EPC-1 in tumor growth and metastasis as an inhibitor of angiogenesis. Overexpression of caspin in murine and human cancer cell lines with a high capability of lung metastasis did not affect the cell growth in vitro, but did significantly suppress both tumor growth in vivo and lung metastasis. The density of microvessels was significantly reduced in tumors formed by s.c. inoculation of cancer cells when caspin was overexpressed, indicating that caspin can cause the inhibition of tumor angiogenesis. In addition, 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.
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