Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth - PubMed (original) (raw)

doi: 10.1016/j.ccr.2006.10.018.

Yvan Chanthery, Wei-Ching Liang, Scott Stawicki, Judy Mak, Nisha Rathore, Raymond K Tong, Joe Kowalski, Sharon Fong Yee, Glenn Pacheco, Sarajane Ross, Zhiyong Cheng, Jennifer Le Couter, Greg Plowman, Franklin Peale, Alexander W Koch, Yan Wu, Anil Bagri, Marc Tessier-Lavigne, Ryan J Watts

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Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth

Qi Pan et al. Cancer Cell. 2007 Jan.

Free article

Abstract

Neuropilin-1 (NRP1) guides the development of the nervous and vascular systems. Binding to either semaphorins or VEGF, NRP1 acts with plexins to regulate neuronal guidance, or with VEGFR2 to mediate vascular development. We have generated two monoclonal antibodies that bind to the Sema- and VEGF-binding domains of NRP1, respectively. Both antibodies reduce angiogenesis and vascular remodeling, while having little effect on other VEGFR2-mediated events. Importantly, anti-NRP1 antibodies have an additive effect with anti-VEGF therapy in reducing tumor growth. Vessels from tumors treated with anti-VEGF show a close association with pericytes, while tumors treated with both anti-NRP1 and anti-VEGF lack this organization. We propose that blocking NRP1 function inhibits vascular remodeling, rendering vessels more susceptible to anti-VEGF therapy.

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