Neuropilin-1 suppresses tumorigenic properties in a human pancreatic adenocarcinoma cell line lacking neuropilin-1 coreceptors
Neuropilin-1 suppresses tumorigenic properties in a human pancreatic adenocarcinoma cell line lacking neuropilin-1 coreceptors
复制标题
DOI：
10.1158/0008-5472.can-04-2229
复制
发表时间：
2005-05-01
期刊：
影响因子：
11.2
通讯作者：
Gallick, GE
中科院分区：
文献类型：
--
作者：
Gray, MJ;Wey, JS;Gallick, GE
神经纤毛蛋白-1（NRP-1）首先被描述为涉及神经元引导的辅助受体，其结合脑信号蛋白/神经纤维蛋白家族的成员。NRP-1也在内皮细胞中表达，并被认为通过与血管内皮生长因子（VEGF）受体2作为共受体而促进血管生成。最近的研究表明，NRP-1可以通过VEGF依赖性和VEGF非依赖性方式发挥作用。NRP-1的表达已在许多人类肿瘤中显示，包括胰腺腺癌。NRP-1在肿瘤细胞中的确切作用尚不清楚，特别是在缺乏NRP-1辅助受体VEGF受体2和丛状蛋白A1的细胞中。为了辨别NRP-1在缺乏这些辅助受体的胰腺癌中的调节作用，我们过表达全长NRP-1和不与脑信号蛋白或VEGF相互作用的NRP-1缺失形式。任何一种亚型的过表达都降低了几种关键的致瘤特性，包括体外非贴壁依赖性细胞生长和迁移，并导致体内肿瘤发病率和肿瘤体积降低。相反，通过小干扰RNA靶向减少NRP-1表达导致肿瘤生长增强。因此，NRP-1可能在不同的肿瘤类型中发挥不同的生长调节作用，改变NRP-1的表达或功能可能是影响胰腺癌生长的一种手段。
Neuropilin-1 (NRP-1) was first described as a coreceptor implicated in neuronal guidance that bound members of the semaphorin/collapsin family. NRP-1 is also expressed in endothelial cells and is believed to promote angiogenesis by acting as a coreceptor with vascular endothelial growth factor (VEGF) receptor 2. Recent studies suggest that NRP-1 can function through both a VEGF-dependent and VEGF-independent fashion. Expression of NRP-1 has been shown in many human tumors, including pancreatic adenocarcinomas. The exact role of NRP-1 in tumor cells is unknown, particularly in cells that lack the NRP-1 coreceptors VEGF receptor 2 and Plexin-A1. To discern the regulatory role(s) of NRP-1 in pancreatic adenocarcinoma that lack these coreceptors, we overexpressed both full-length NRP-1 and a deletion form of NRP-1 that does not interact with semaphorin or VEGF. Overexpression of either isoform reduced several key tumorigenic properties, including anchorage-independent cell growth and migration in vitro, and resulted in reduced tumor incidence and tumor volume in vivo. Conversely, reduction of NRP-1 expression by small interfering RNA targeting led to enhanced tumor growth. Thus, NRP-1 may play distinct growth regulatory roles in different tumor types, and altering NRP-1 expression or function may be a means of influencing the growth of pancreatic cancers.