Neuropilin 1 (NRP1), a receptor of vascular endothelial growth factor (VEGF), promotes angiogenesis, tumor growth, tumor invasion and metastasis.,However, the function of NRP1 in melanoma progression, as well as the effect of NRP1 expression on the prognosis of patients with melanoma remains unknown.,In the present study, NRP1 expression was examined in 460 cases of melanocytic lesions (28 common nevi, 51 dysplastic nevi, 250 primary melanoma and 131 metastatic melanoma) at different stages, using a tissue microarray.,The correlation of NRP1 expression with melanoma progression, and its prognostic value in patients with melanoma was examined.,In addition, the correlation between matrix metalloproteinase 2 (MMP2) and NRP1 expression in patients with melanoma was analyzed.,The results demonstrated that NRP1 expression was significantly increased in primary (56%) and metastatic melanoma (62%), compared with common nevi (11%) and dysplastic nevi (24%).,Notably, increased NRP1 expression was correlated with a poorer overall, and disease specific, 10-year survival (P=0.03 and P=0.002, respectively).,Multivariate Cox regression analyses indicated that NRP1 is an independent prognostic marker for melanoma.,Furthermore, a significant positive correlation between NRP1 and MMP2 expression in melanoma biopsies was observed, and their concomitant expression was closely correlated with melanoma patient survival, further supporting the hypothesis that the expression of NRP1 is associated with melanoma invasion and metastasis.,In conclusion, increased NRP1 expression is associated with disease progression and reduced survival in patients with melanoma, and is a promising prognostic molecular marker for this disease.
Semaphorins are secreted and membrane bound proteins involved in neural pathfinding, organogenesis, and tumor progression, through Plexin and neuropilins receptors.,We recently reported that Plexin B1, the Semaphorin 4D receptor, is a tumor suppressor protein for melanoma, in part, through inhibition of the oncogenic c-Met tyrosine kinase receptor.,In this report we show that Sema4D is a protective paracrine factor for normal human melanocyte survival in response to ultraviolet irradiation, that it stimulates proliferation, and regulates the activity of the c-Met receptor. c-Met receptor signaling stimulates melanocyte migration, in part through down-regulation of the cell adhesion molecule E-cadherin.,Sema4D suppressed activation of c-Met in response to its ligand hepatocyte growth factor (HGF), and partially blocked the suppressive effects of HGF on E-cadherin expression in melanocytes and HGF-dependent migration.,These data demonstrate a role for Plexin B1 in maintenance of melanocyte survival and proliferation in the skin, and suggest that Semaphorin 4D and Plexin B1 act cooperatively with HGF and c-Met to regulate c-Met dependent effects in human melanocytes.,Because our data show that Plexin B1 is profoundly down-regulated by UVB in melanocytes, loss of Plexin B1 may accentuate HGF dependent effects on melanocytes, including melanocyte migration.