Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors

Reynolds, Andrew R., Hart, Ian R., Watson, Alan R., Welti, Jonathan C., Silva, Rita G., Robinson, Stephen D., Da Violante, Georges, Gourlaouen, Morgane, Salih, Mishal, Jones, Matt C., Jones, Dylan T., Saunders, Garry, Kostourou, Vassiliki, Perron-Sierra, Françoise, Norman, Jim C., Tucker, Gordon C. and Hodivala-Dilke, Kairbaan M. (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nature Medicine, 15 (4). pp. 392-400. ISSN 1078-8956

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Abstract

Inhibitors of alphavbeta3 and alphavbeta5 integrin have entered clinical trials as antiangiogenic agents for cancer treatment but generally have been unsuccessful. Here we present in vivo evidence that low (nanomolar) concentrations of RGD-mimetic alphavbeta3 and alphavbeta5 inhibitors can paradoxically stimulate tumor growth and tumor angiogenesis. We show that low concentrations of these inhibitors promote VEGF-mediated angiogenesis by altering alphavbeta3 integrin and vascular endothelial growth factor receptor-2 trafficking, thereby promoting endothelial cell migration to VEGF. The proangiogenic effects of low concentrations of RGD-mimetic integrin inhibitors could compromise their efficacy as anticancer agents and have major implications for the use of RGD-mimetic compounds in humans.

Item Type: Article
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Users 2731 not found.
Date Deposited: 22 Nov 2011 13:59
Last Modified: 21 Apr 2020 17:29
URI: https://ueaeprints.uea.ac.uk/id/eprint/35534
DOI: 10.1038/nm.1941

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