title: Neuropilin-1 as Therapeutic Target for Malignant Melanoma.
abstract: 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.
authors.affiliation: Department of Systems Medicine, University of Rome "Tor Vergata" , Rome , Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Graziani
authors.affiliation: Laboratory of Molecular Oncology, "Istituto Dermopatico dell'Immacolata", Istituto di Ricovero e Cura a Carattere Scientifico , Rome , Italy.
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Lacal
keywords: T regulatory cells; angiogenesis; cell-penetrating peptides; melanoma; metastasis; neuropilin-1; peptidomimetics