Chondroitin sulfate proteoglycan 4 (CSPG4), a transmembrane
proteoglycan originally identified as a highly immunogenic
tumor antigen on the surface of
melanoma cells, is associated with
melanoma tumor formation and poor prognosis in certain
melanomas and several other
tumor types. The complex mechanisms by which CSPG4 affects
melanoma progression have started to be defined, in particular the association with other
cell surface proteins and
receptor tyrosine kinases (RTKs) and its central role in modulating the function of these
proteins. CSPG4 is essential to the growth of
melanoma tumors through its modulation of
integrin function and enhanced
growth factor receptor-regulated pathways including sustained activation of ERK 1,2. This activation of
integrin, RTK, and ERK1,2 function by CSPG4 modulates numerous aspects of
tumor progression. CSPG4 expression has further been correlated to resistance of
melanoma to conventional chemotherapeutics. This review outlines recent advances in our understanding of CSPG4-associated cell signaling, describing the central role it plays in
melanoma tumor cell growth, motility, and survival, and explores how modifying CSPG4 function and
protein-
protein interactions may provide us with novel combinatorial
therapies for the treatment of advanced
melanoma.