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

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caspin可明显抑制大鼠主动脉微血管的离体生长和体外培养内皮细胞的生长，并呈剂量依赖性。此外，我们发现caspin可以特异性地诱导内皮细胞凋亡，而对其他类型的培养细胞没有作用。这些发现表明caspin/PEDF/EPC-1通过诱导内皮细胞凋亡调节血管生成。因此，该蛋白可能在重要的生物事件中起着至关重要的作用，在这些事件中，组织重建和突出的血管生成是必不可少的，如胚胎发生、伤口愈合、肉芽组织的形成以及肿瘤的生长和转移。

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.