Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth
Blocking neuropilin-1 function has an additive effect with anti-VEGF to inhibit tumor growth
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DOI：
10.1016/j.ccr.2006.10.018
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发表时间：
2007-01-01
期刊：
影响因子：
50.3
通讯作者：
Watts, Ryan J.
中科院分区：
文献类型：
--
作者：
Pan, Qi;Chanthery, Yvan;Watts, Ryan J.
神经纤毛蛋白-1（NRP 1）指导神经和血管系统的发育。NRP 1与脑信号蛋白或VEGF结合，与丛蛋白一起调节神经元引导，或与VEGFR 2一起介导血管发育。我们已经产生了两种单克隆抗体，分别结合到NRP 1的Sema和VEGF结合域。这两种抗体都减少血管生成和血管重塑，而对其他VEGFR 2介导的事件几乎没有影响。重要的是，抗NRP 1抗体与抗VEGF治疗在减少肿瘤生长方面具有累加效应。来自用抗VEGF治疗的肿瘤的血管显示与周细胞密切相关，而用抗NRP 1和抗VEGF治疗的肿瘤缺乏这种组织。我们认为，阻断NRP 1功能可以抑制血管重塑，使血管更容易对抗VEGF治疗。
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.