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Blood, 15 August 2006, Vol. 108, No. 4, pp. 1243-1250.
Prepublished online as a Blood First Edition Paper on April 18, 2006; DOI 10.1182/blood-2005-11-4447.
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Submitted November 10, 2005
Accepted March 27, 2006
Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cells survival and migration
Benoit Favier, Antoine Alam, Pauline Barron, Jacques Bonnin, Patricia Laboudie, Pierre Fons, Marie Mandron, Jean-Pascal Herault, Gera Neufeld, Pierre Savi, Jean-Marc Herbert, and Francoise Bono*
Angiogenesis and Thrombosis Department, Sanofi~Synthelabo Research, Toulouse, France
Bruce Rappaport Faculty of Medicine, Technion, Israel Institute of Technology, Haifa, Israel
* Corresponding author; email: francoise.bono{at}sanofi-aventis.com.
Neuropilin-2 (NRP-2) is a receptor for the Vascular Endothelial Growth Factor (VEGF) and the Semaphorin (Sema) families, two unrelated ligand families involved in angiogenesis and neuronal guidance. NRP-2 binds specifically VEGF-A and VEGF-C, however the biological relevance of these interactions in human endothelial cells is poorly understood. In this study, we show that both VEGF-A and VEGF-C induce the interaction of NRP-2 with VEGFR-2. This interaction correlated with an enhancement of the VEGFR-2 phosphorylation threshold. Overexpression of NRP-2 in primary human endothelial cells promoted cell survival induced by VEGF-A and VEGF-C. In contrast, the Sema-3F, another ligand for NRP-2, was able to inhibit human endothelial cell survival and migration induced by VEGF-A and VEGF-C. Moreover, a siRNA targeting specifically NRP-2 is a potent inhibitor of human endothelial cell migration induced by VEGF-A and VEGF-C. Thus, our data indicate that NRP-2 acts as a co-receptor that enhances human endothelial cell biological responses induced by VEGF-A and VEGF-C.
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