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

Favier B, Alam A, Barron P, Bonnin J, Laboudie P, Fons P, Mandron M, Herault JP, Neufeld G, Savi P, Herbert JM, Bono F
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
Nucleofector® I/II/2b
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.