Neuropilin-1 as Therapeutic Target for Malignant Melanoma.
Neuropilin-1 as Therapeutic Target for Malignant Melanoma.
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DOI：
10.3389/fonc.2015.00125
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发表时间：
2015
影响因子：
4.7
通讯作者：
Lacal PM
中科院分区：
文献类型：
--
作者：
Graziani G;Lacal PM
神经纤毛蛋白-1（NRP-1）是一种跨膜糖蛋白，作为血管内皮生长因子（VEGF）家族各种成员的共受体。其结合或调节许多其他细胞外配体（例如3类脑信号蛋白、TGF-β、HGF、FGF和PDGF）的活性的能力表明NRP-1参与多种生理和病理过程。事实上，这种辅助受体与轴突导向、血管生成和免疫反应有关。NRP-1还在多种癌症（前列腺癌、肺癌、胰腺癌或结肠癌、黑色素瘤、星形细胞瘤、胶质母细胞瘤和神经母细胞瘤）中表达，表明在肿瘤进展中起关键作用。此外，越来越多的证据表明，NRP-1可能独立于其他VEGF受体发挥重要功能。特别地，在不存在VEGFR-1/2的情况下，NRP-1通过刺激VEGF-A和金属蛋白酶分泌并调节特异性信号转导途径，通过活化选定的整联蛋白来促进黑素瘤侵袭性。本文综述了NRP-1在黑色素瘤侵袭性中的作用以及支持其作为转移性黑色素瘤治疗靶点的证据。
Neuropilin-1 (NRP-1) is a transmembrane glycoprotein that acts as a co-receptor for various members of the vascular endothelial growth factor (VEGF) family. Its ability to bind or modulate the activity of a number of other extracellular ligands, such as class 3 semaphorins, TGF-β, HGF, FGF, and PDGF, has suggested the involvement of NRP-1 in a variety of physiological and pathological processes. Actually, this co-receptor has been implicated in axon guidance, angiogenesis, and immune responses. NRP-1 is also expressed in a variety of cancers (prostate, lung, pancreatic, or colon carcinoma, melanoma, astrocytoma, glioblastoma, and neuroblastoma), suggesting a critical role in tumor progression. Moreover, a growing amount of evidence indicates that NRP-1 might display important functions independently of other VEGF receptors. In particular, in the absence of VEGFR-1/2, NRP-1 promotes melanoma invasiveness, through the activation of selected integrins, by stimulating VEGF-A and metalloproteinases secretion and modulating specific signal transduction pathways. This review is focused on the role of NRP-1 in melanoma aggressiveness and on the evidence supporting its use as target of therapies for metastatic melanoma.
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