Evaluating The Role Of b3‐Integrins In Angiogenesis

Inhibition of avb3 or avb5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Results. We have reported that mice lacking b3integrins or both b3 and b5 integrins not only support tumorigenesis, but have enhanced tumor growth as well. Moreover, the tumors in these integrin‐ deficient mice display enhanced angiogenesis, strongly suggesting that neither b3 nor b5 integrins are essential for neovascularization. We have evidence that this enhanced angiogenesis is not due to compensation by other integrins but by the upregulation of Flk‐1 expression and function. Moreover, antagonists of avb3 and avb5 integrins, that are in being tested as anti‐angiogenic agents, show a biphasic effect on angiogenesis: at high concentrations they inhibit angiogenesis, but at low concentrations they enhance it. Conclusions These data indicate that avb3 and avb5 integrins are not essential for pathological angiogenesis and highlight the need for further evaluation of the method of administration of av‐integrin antagonists in anti‐angiogenic therapeutics. This work is supported by Cancer Research UK.