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Blood, 1 March 2005, Vol. 105, No. 5, pp. 1992-1999.
Prepublished online as a Blood First Edition Paper on November 2, 2004; DOI 10.1182/blood-2004-07-2598.
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Submitted July 8, 2004
Accepted October 28, 2004
Neuropilin-1 regulates attachment in human endothelial cells independently of vascular endothelial growth factor receptor-2
Matilde Murga*, Oscar Fernandez-Capetillo, and Giovanna Tosato
Experimental Transplantation and Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
* Corresponding author; email: costama{at}mail.nih.gov.
Neuropilin-1 (NRP-1) is a type 1 membrane protein that binds the axon guidance factors belonging to the class-3 semaforin family. In endothelial cells, NRP-1 serves as a co-receptor for vascular endothelial growth factor (VEGF) and regulates VEGF receptor (R)-2-dependent angiogenesis. Though gene-targeting studies documenting embryonic lethality in NRP-1 null mice have demonstrated a critical role for NRP-1 in vascular development, the activities of NRP-1 in mature endothelial cells have been incompletely defined. Using RNA interference-mediated silencing of NRP-1 or VEGFR-2 in primary human endothelial cells we confirm that NRP-1 modulates VEGFR-2 signaling-dependent mitogenic functions of VEGF. Importantly, we now show that NRP-1 regulates endothelial cell adhesion to extra-cellular matrix proteins independently of VEGFR-2. Based on its dual role as an enhancer of VEGF activity and a mediator of endothelial cell adhesiveness described here, NRP-1 emerges as a promising molecular target for the development of anti-angiogenic drugs.

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