Targeted inhibition of αvβ3 integrin with an RNA aptamer impairs endothelial cell growth and survival^,

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• 作者：Jing Mi ; Xiuwu Zhang ; Paloma H. Giangrande ; James O. McNamara II ; Shahid M. Nimjee ; Shiva Sarraf-Yazdi ; Bruce A. Sullenger and Bryan M. Clary
• 关键词：α ; vβ ; 3 integrin ; Aptamer ; Endothelial cells ; Apoptosis ; Angiogenesis
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2005
• 出版时间：16 December 2005
• 年：2005
• 卷：338
• 期：2
• 页码：956-963
• 全文大小：255 K

文摘

αvβ3 integrin is a crucial factor involved in a variety of physiological processes, such as cell growth and migration, tumor invasion and metastasis, angiogenesis, and wound healing. αvβ3 integrin exerts its effect by regulating endothelial cell (EC) migration, proliferation, and survival. Inhibiting the function of αvβ3 integrin, therefore, represents a potential anti-cancer, anti-thrombotic, and anti-inflammatory strategy. In this study, we tested an RNA aptamer, Apt-αvβ3 that binds recombinant αvβ3 integrin, for its ability to bind endogenous αvβ3 integrin on the surface of cells in culture and to subsequently affect cellular response. Our data illustrate that Apt-αvβ3 binds αvβ3 integrin expressed on the surface of live HUVECs. This interaction significantly decreases both basal and PDGF-induced cell proliferation as well as inhibition of cell adhesion. Apt-αvβ3 can also reduce PDGF-stimulated tube formation and increase HUVEC apoptosis through inhibition of FAK phosphorylation pathway. Our results demonstrate that by binding to its target, Apt-αvβ3 can efficiently inhibit human EC proliferation and survival, resulting in reduced angiogenesis. It predicts that Apt-αvβ3 could become useful in both tumor imaging and the treatment of tumor growth, atherosclerosis, thrombosis, and inflammation.