Miao H Q, Lee P, Lin H, Soker S, Klagsbrun M
Department of Surgical Research, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
FASEB J. 2000 Dec;14(15):2532-9. doi: 10.1096/fj.00-0250com.
Neuropilin-1 (NRP1) is a VEGF(165) and semaphorin receptor expressed by vascular endothelial cells (EC) and tumor cells. The function of NRP1 in tumor cells is unknown. NRP1 was overexpressed in Dunning rat prostate carcinoma AT2.1 cells using a tetracycline-inducible promoter. Concomitant with increased NRP1 expression in response to a tetracycline homologue, doxycycline (Dox), basal cell motility, and VEGF(165) binding were increased three- to fourfold in vitro. However, induction of NRP1 did not affect tumor cell proliferation. When rats injected with AT2.1/NRP1 tumor cells were fed Dox, NRP1 synthesis was induced in vivo and AT2.1 cell tumor size was increased 2.5- to 7-fold in a 3-4 wk period compared to controls. The larger tumors with induced NRP1 expression were characterized by markedly increased microvessel density, increased proliferating EC, dilated blood vessels, and notably less tumor cell apoptosis compared to noninduced controls. It was concluded that NRP1 expression results in enlarged tumors associated with substantially enhanced tumor angiogenesis.
神经纤毛蛋白-1（NRP1）是一种由血管内皮细胞（EC）和肿瘤细胞表达的血管内皮生长因子（VEGF）（165）和信号素受体。NRP1在肿瘤细胞中的功能尚不清楚。使用四环素诱导型启动子在邓宁大鼠前列腺癌AT2.1细胞中过表达NRP1。与响应四环素类似物强力霉素（Dox）而增加的NRP1表达相伴，基础细胞运动性和VEGF（165）结合在体外增加了三到四倍。然而，NRP1的诱导并不影响肿瘤细胞增殖。当给注射了AT2.1/NRP1肿瘤细胞的大鼠喂食Dox时，体内诱导了NRP1合成，与对照组相比，在3-4周的时间内AT2.1细胞肿瘤大小增加了2.5至7倍。与未诱导的对照组相比，诱导了NRP1表达的较大肿瘤的特征是微血管密度显著增加、增殖的EC增加、血管扩张以及肿瘤细胞凋亡明显减少。得出的结论是，NRP1表达导致肿瘤增大并伴有肿瘤血管生成显著增强。
