Integrin alpha(v)beta(3)-mediated activation of apoptosis

The alpha(v)beta(3) integrin mediates endothelial cell binding to the extra cellular matrix and transduces an intracellular signal promoting survival o f endothelial cells and various tumor cells. While the alpha(v)beta(3) inte grin-mediated survival signal has been shown to be adhesion dependent, a th orough 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 expre ssion of alpha(v)beta(3) integrin in human embryonic kidney 293 cells trans fers the alpha(v)beta(3) integrin survival pathway to an epithelial cell li ne. Furthermore, we show that alpha(v)beta(3) integrin-expressing cells res pond differently to alpha(v)beta(3) integrin-specific antagonist treatment and growth in suspension conditions. Treatment with the alpha(v)beta(3) ant agonist echistatin resulted in an apoptotic response occurring prior to cel l detachment and was not observed in either suspended cells or antagonist-t reated suspended cells. These data suggest that the death induced by antago nist binding to alpha(v)beta(3) integrin results in an apoptotic signal wit h different kinetics than the apoptotic signal induced by matrix detachment (anoikis). Since aberrant alpha(v)beta(3) integrin expression in tumor mod els is thought to play a role in tumor cell survival, these data have impli cations for the use of alpha(v)beta(3) antagonists as anti-tumor agents. (C ) 1999 Academic Press.