CSPG4, a potential therapeutic target, facilitates malignant progression of melanoma

Abstract

Summary 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 ERK 1,2 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.

NG2 proteoglycan-dependent recruitment of tumor macrophages promotes pericyte-endothelial cell interactions required for brain tumor vascularization

“…However, the proteoglycan is also expressed by tumor cells in several types of cancer, including melanoma, [41][42][43][44] glioblastoma, 38,45,46 sarcoma, 47 myeloid leukemia, 48 and triple-negative breast cancer. 49 In all cases, increased NG2 expression by tumor cells is associated with enhanced tumor progression and worsened patient prognosis.…”

Extracellular matrix component signaling in cancer

“…It is a marker of vascular mural cells, and is highly upregulated in melanoma, where it may contribute to invasive behaviour. The mechanisms involve activation of RTKs with sustained ERK1,2 signalling, and integrins [175]. This theme is common to other cell surface proteoglycans, e.g.…”

CSPG4-Specific Immunity and Survival Prolongation in Dogs with Oral Malignant Melanoma Immunized with Human CSPG4 DNA

“…Chondroitin sulfate proteoglycan-4 (CSPG4), an early cell surface progression marker involved in tumor cell proliferation, migration, and invasion meets these criteria (16). The induction of CSPG4-specific antibodies in patients with melanoma that have been immunized with CSPG4 mimics has been associated with significantly longer survival and metastases regression, highlighting the potential clinical relevance of this tumor antigen as a target for antibody-based immunotherapy (17,18).…”