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

Andrew R. Reynolds | Zendy; Ian R. Hart | Zendy; Alan R. Watson | Zendy; Jonathan Welti | Zendy; Rita G Silva | Zendy; Stephen D. Robinson | Zendy; Georges Da Violante | Zendy; Morgane Gourlaouen | Zendy; Mishal Salih | Zendy; Matt Jones | Zendy; Dylan T. Jones | Zendy; G Saunders | Zendy; Vassiliki Kostourou | Zendy; Francoise PerronSierra | Zendy; Jim C. Norman | Zendy; Gordon C. Tucker | Zendy; Kairbaan HodivalaDilke | Zendy

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

Author(s) -

Andrew R. Reynolds,

Ian R. Hart,

Alan R. Watson,

Jonathan Welti,

Rita G Silva,

Stephen D. Robinson,

Georges Da Violante,

Morgane Gourlaouen,

Mishal Salih,

Matt Jones,

Dylan T. Jones,

G Saunders,

Vassiliki Kostourou,

Francoise PerronSierra,

Jim C. Norman,

Gordon C. Tucker,

Kairbaan HodivalaDilke

Publication year - 2009

Publication title -

nature medicine

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 19.536

H-Index - 547

eISSN - 1546-170X

pISSN - 1078-8956

DOI - 10.1038/nm.1941

Subject(s) - angiogenesis , integrin , cancer research , alpha (finance) , in vivo , stimulation , pharmacology , alpha v beta 3 , vascular endothelial growth factor , endothelial stem cell , cell growth , medicine , chemistry , vegf receptors , microbiology and biotechnology , receptor , biology , in vitro , endocrinology , vitronectin , biochemistry , surgery , construct validity , patient satisfaction

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.

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