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

Reynolds, A.R. et al. (2009) Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nature Medicine, 15(4), pp. 392-400. (doi: 10.1038/nm.1941)

Abstract

Inhibitors of alpha(v)beta(3) and alpha(v)beta(5) 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 alpha(v)beta(3) and alpha(v)beta(5) inhibitors can paradoxically stimulate tumor growth and tumor angiogenesis. We show that low concentrations of these inhibitors promote VEGF-mediated angiogenesis by altering alpha(v)beta(3) 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: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Norman, Professor James and Jones, Mr Matthew
• Authors: Reynolds, A.R., Hart, I.R., Watson, A.R., Welti, J.C., Silva, R.G., Robinson, S.D., Da Violante, G., Gourlaouen, M., Salih, M., Jones, M.C., Jones, D.T., Saunders, G., Kostourou, V., Perron-Sierra, F., Norman, J.C., Tucker, G.C., and Hodivala-Dilke, K.M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Nature Medicine
• ISSN: 1078-8956