Enhanced pathological angiogenesis in mice lacking 3 integrin or 3 and 5 integrins
Louise E. Reynolds1, 4, Lorenza Wyder1, 4, Julie C. Lively2, Daniela Taverna2, Stephen D. Robinson1, Xiaozhu Huang3, Dean Sheppard3, Richard O. Hynes2
& Kairbaan M. Hodivala-Dilke1
1
Cell Adhesion and Disease Laboratory, Richard Dimbleby Department, Imperial Cancer Research Fund, St. Thomas' Hospital, London, UK
2
Howard Hughes Medical Institute, Center for Cancer Research, MIT, Cambridge, Massachusetts 02139 USA
3
Lung Biology Center, University of California, San Francisco, California, USA
4
L.E.R. and L.W. contributed equally to this study.
Inhibition of v3 or v5 integrin function has been reported to suppress neovascularization and tumor growth, suggesting that these integrins are critical modulators of angiogenesis. Here we report that mice lacking 3 integrins or both 3 and 5 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 3 nor 5 integrins are essential for neovascularization. We also observed that angiogenic responses to hypoxia and vascular endothelial growth factor (VEGF) are augmented significantly in the absence of 3 integrins. We found no evidence that the expression or functions of other integrins were altered as a consequence of the 3 deficiency, but we did observe elevated levels of VEGF receptor-2 (also called Flk-1) in 3-null endothelial cells. These data indicate that v3 and v5 integrins are not essential for vascular development or pathological angiogenesis and highlight the need for further evaluation of the mechanisms of action of v-integrin antagonists in anti-angiogenic therapeutics.
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
3 integrin or 
v
3 or 
