Pan Qi, Chanthery Yvan, Liang Wei-Ching, Stawicki Scott, Mak Judy, Rathore Nisha, Tong Raymond K, Kowalski Joe, Yee Sharon Fong, Pacheco Glenn, Ross Sarajane, Cheng Zhiyong, Le Couter Jennifer, Plowman Greg, Peale Franklin, Koch Alexander W, Wu Yan, Bagri Anil, Tessier-Lavigne Marc, Watts Ryan J
Tumor Biology and Angiogenesis, Genentech, Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Cancer Cell. 2007 Jan;11(1):53-67. doi: 10.1016/j.ccr.2006.10.018.
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.
神经纤毛蛋白-1（NRP1）指导神经和血管系统的发育。NRP1与信号素或血管内皮生长因子（VEGF）结合，与丛状蛋白共同作用调节神经元导向，或与血管内皮生长因子受体2（VEGFR2）共同作用介导血管发育。我们制备了两种单克隆抗体，分别与NRP1的信号素结合域和VEGF结合域结合。两种抗体均能减少血管生成和血管重塑，而对其他VEGFR2介导的事件影响很小。重要的是，抗NRP1抗体与抗VEGF疗法在减少肿瘤生长方面具有相加作用。用抗VEGF治疗的肿瘤血管与周细胞紧密相关，而用抗NRP1和抗VEGF联合治疗的肿瘤则缺乏这种组织结构。我们提出，阻断NRP1功能可抑制血管重塑，使血管对抗VEGF疗法更敏感。
