Integrin αvβ3-mediated activation of apoptosis
Integrin αvβ3-mediated activation of apoptosis
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DOI：
10.1006/excr.1999.4559
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发表时间：
1999-08-25
影响因子：
3.7
通讯作者：
Armstrong, L
中科院分区：
文献类型：
--
作者：
Brassard, DL;Maxwell, E;Armstrong, L
α(V)β(3)整合素介导内皮细胞与细胞外基质的结合，并传递促进内皮细胞和各种肿瘤细胞存活的细胞内信号。虽然α(V)β(3)整合素介导的生存信号已被证明是黏附依赖的，但尚未有深入的分析比较拮抗剂与α(V)β(3)整合素结合的生化效应与悬浮细胞生长诱导的效应。在这项研究中，我们证明了在人胚胎肾脏293细胞中表达α(V)β(3)整合素将α(V)β(3)整合素的生存途径转移到上皮细胞系。此外，我们发现，在悬浮条件下，表达整合素α(V)β(3)的细胞对α(V)β(3)整合素特异性拮抗剂处理和生长的反应不同。用α(V)β(3)拮抗剂ecstaatin处理后，在细胞脱离之前发生了一种凋亡反应，在悬浮细胞或经拮抗剂处理的悬浮细胞中都没有观察到。这些数据表明，拮抗剂与α(V)β(3)整合素结合诱导的死亡导致的凋亡信号与基质脱离(Anikis)诱导的凋亡信号的动力学不同。由于肿瘤模型中α(V)β(3)整合素的异常表达被认为在肿瘤细胞存活中发挥作用，这些数据对使用α(V)β(3)拮抗剂作为抗肿瘤药物具有一定的意义。(C)1999年学术出版社。
The alpha(v)beta(3) integrin mediates endothelial cell binding to the extracellular matrix and transduces an intracellular signal promoting survival of endothelial cells and various tumor cells. While the alpha(v)beta(3) integrin-mediated survival signal has been shown to be adhesion dependent, a thorough analysis has not been performed comparing the biochemical effects of antagonist binding to alpha(v)beta(3) integrin with the effects induced by the growth of cells in suspension. In this study we demonstrate that expression of alpha(v)beta(3) integrin in human embryonic kidney 293 cells transfers the alpha(v)beta(3) integrin survival pathway to an epithelial cell line. Furthermore, we show that alpha(v)beta(3) integrin-expressing cells respond differently to alpha(v)beta(3) integrin-specific antagonist treatment and growth in suspension conditions. Treatment with the alpha(v)beta(3) antagonist echistatin resulted in an apoptotic response occurring prior to cell detachment and was not observed in either suspended cells or antagonist-treated suspended cells. These data suggest that the death induced by antagonist binding to alpha(v)beta(3) integrin results in an apoptotic signal with different kinetics than the apoptotic signal induced by matrix detachment (anoikis). Since aberrant alpha(v)beta(3) integrin expression in tumor models is thought to play a role in tumor cell survival, these data have implications for the use of alpha(v)beta(3) antagonists as anti-tumor agents. (C) 1999 Academic Press.