Integrin αvβ3-Mediated Activation of Apoptosis

Abstract The α v β 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 α v β 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 α v β 3 integrin with the effects induced by the growth of cells in suspension. In this study we demonstrate that expression of α v β 3 integrin in human embryonic kidney 293 cells transfers the α v β 3 integrin survival pathway to an epithelial cell line. Furthermore, we show that α v β 3 integrin-expressing cells respond differently to α v β 3 integrin-specific antagonist treatment and growth in suspension conditions. Treatment with the α v β 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 α v β 3 integrin results in an apoptotic signal with different kinetics than the apoptotic signal induced by matrix detachment (anoikis). Since aberrant α v β 3 integrin expression in tumor models is thought to play a role in tumor cell survival, these data have implications for the use of α v β 3 antagonists as anti-tumor agents.