Neuropilin-2 interacts with VEGFR-2 and VEGFR-3 and promotes human endothelial cells survival and migration

Authors:
Favier B, Alam A, Barron P, Bonnin J, Laboudie P, Fons P, Mandron M, Herault JP, Neufeld G, Savi P, Herbert JM, Bono F
In:
Source: Blood
Publication Date: (2006)
Issue: 108(4): 1243-50
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Endothelial, MV lung, human (HMVEC-L)
Species: human
Tissue Origin: lung
Platform:
Nucleofectorâ„¢ I/II/2b
Abstract
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.