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.