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

Caspin/PEDF/EPC-1 通过特异性诱导内皮细胞凋亡来抑制肿瘤生长和转移

• 批准号: 12671975
• 负责人: KAWAI Toshihiko
• 金额: $ 1.92万
• 依托单位: Aichi-Gakuin University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671975/
• 关键词: caspin; PEDF; EPC-1; apoptosis; endothelial cell; angiogenesis; tumor growth; tumor metastasis; apoptosis

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.

我们研究了Caspin/PEDF/EPC-1作为血管生成抑制剂在肿瘤生长和转移中的生理和病理生理作用。在培养物中添加重组半胱氨酸天冬氨酸蛋白明显抑制离体大鼠主动脉微血管的生长和培养的内皮细胞的体外生长，并呈剂量依赖性。此外，我们发现，半胱天冬肽可以诱导凋亡，特别是在内皮细胞，而不是在任何其他类型的培养细胞。这些结果表明，Caspin/PEDF/EPC-1通过诱导内皮细胞凋亡来调节血管生成。因此，这种蛋白质可能在重要的生物学事件中发挥至关重要的作用，其中基本上需要具有显著血管生成的组织重建，例如胚胎发生、伤口愈合和肉芽组织的形成以及肿瘤生长和转移。

项目成果

Azuma, M., et al.: "A synthetic peptide of human apoprotein E with antibacterial activity."Peptides. 21. 327-330 (2000)

Azuma, M., et al.：“具有抗菌活性的人脱辅基蛋白 E 的合成肽。”肽。

Nakayashiki,N., et al.: "Production of a single-chain variable fragment antibody recognizing type III mutant epidermal growth factor receptor."Jpn.J.Cancer Res.. 91. 1035-1043 (2000)

Nakayashiki,N.等人：“识别III型突变表皮生长因子受体的单链可变片段抗体的生产”。Jpn.J.Cancer Res.. 91. 1035-1043 (2000)

Tsujimura, K., Obata, Y., Matsudaira, Y., Ozeki, S., Yoshikawa, K., Saga, S., Takahashi, T.: "The binding of thymus leukemia (TL) antigen tetramers to normal intestinal intraepithelial lymphocytes and thymocytes"J Immunol.. 167. 759-764 (2001)

Tsujimura, K.、Obata, Y.、Matsudaira, Y.、Ozeki, S.、Yoshikawa, K.、Saga, S.、Takahashi, T.：“胸腺白血病 (TL) 抗原四聚体与正常肠上皮内的结合

Nakayashiki, N., Yoshikawa, K., Nakamura, K., Hanai, N., Okamoto, K., Okamoto, S., Mizuno, M., Wakabayashi, T., Saga, S., Yoshida, J. and Takahashi, T.: "Production of a single-chain variable fragment antibody recognizing type III mutant epidermal growth

Nakayashiki, N.、Yoshikawa, K.、Nakamura, K.、Hanai, N.、Okamoto, K.、Okamoto, S.、Mizuno, M.、Wakabayashi, T.、Saga, S.、Yoshida, J. 和

Azuma, M., Kojimab, T., Yokoyama, I., Tajiri, H., Yoshikawa, K., Saga, S.and Del, Carpio, CA.: "A synthetic peptide of human apoprotein E with antibacterial activity."Peptides. 21. 327-330 (2000)

Azuma, M.、Kojimab, T.、Yokoyama, I.、Tajiri, H.、Yoshikawa, K.、Saga, S. 和 Del, Carpio, CA.：“具有抗菌活性的人类脱辅基蛋白 E 的合成肽。”