Neuropilin-1及其作为恶性肿瘤治疗靶点的研究进展

Advances in neuropilin-1 and its role as a therapeutic target in treatment of malignancies

神经纤毛蛋白1(neuropilin-1,NRP-1)是一种跨膜糖蛋白。它作为血管内皮生长因子(vascular endothelial growth factor,VEGF)家族的一个共受体,能结合或调节一些其他细胞外配体,如第3类神经生长导向因子(class 3 semaphorins,Sema3s)、转化生长因子β(transforming growth factor-β,TGF-β)、肝细胞生长因子(hepatocyte growth factor,HGF)、成纤维生长因子(i broblast growth factors,FGF)和血小板衍生因子(platelet derived growth factor,PDGF),从而参与轴突导向、血管形成和免疫反应等多种生理和病理过程。NRP-1在多种肿瘤(如黑素瘤、前列腺癌、肺癌、胰腺癌、结肠癌、星形细胞瘤、成胶质细胞瘤和成神经细胞瘤)细胞中异常表达,进而在肿瘤的发生和发展过程中起关键作用。许多研究表明,NRP-1可以不依赖VEGF受体而显示出重要功能。当缺乏VEGF受体1/2时,NRP-1可通过激活选择性整合素,刺激VEGF-A和金属蛋白酶的分泌,调节特定的信号转导通路,最终促进黑素瘤的侵袭和转移。本文以黑素瘤为重点,探讨NRP-1在肿瘤侵袭和转移中的作用以及以NRP-1为靶点治疗恶性肿瘤的相关研究进展。

Neuropilin-1（NRP-1） is a transmembrane glycoprotein which acts as a co-receptor for various members of vascular endothelial growth factor（VEGF） family.It can bind or modulate a number of other extracellular ligands,such as class 3 semaphorins（Sema3s）,transforming growth factor-β（TCF-β）,hepatocyte growth factor（HGF）,fibroblast growth factor（FGF）,and platelet-derived growth factor（PDGF）.NRP-1 is involved in many physiological and pathological processes such as axon guidance,angiogenesis and immune response.NRP-1 is also expressed in a variety of cancer cells（such as melanoma,prostate cancer,lung cancer,pancreatic carcinoma,colon carcinoma,astrocytoma,glioblastoma and neuroblastoma cells）,suggesting that it plays a critical role in cancer progression.Moreover,a growing amount of evidence shows that NRP-1 might display important functions and do not rely on other VEGF receptors（VEGFRs）.In the absence of VEGFR-1/2,NRP-1 promotes the invasion and metastasis of melanoma through activating the selected integrins,stimulating the secretion of VEGF-A and metalloproteinases,and modulating specific signal transduction pathways.This article focuses on the role of NRP-1 in the invasion and metastasis of malignancies and overviews the research progress in NRP-1 as a target in the treatment of malignancies,especially about melanoma.