CSPG4

Chondroitin sulfate proteoglycan 4 (CSPG4), also known as neuron-glial antigen 2 (NG2) or high molecular weight melanoma-associated antigen (HMW-MAA), is a transmembrane proteoglycan expressed on proliferating glial precursors, pericytes, and aggressive malignancies. Functionally, CSPG4 mediates cell proliferation, migration, and angiogenesis through interactions with integrins (α4β1, αVβ3) and growth factor receptors (PDGFRα, EGFR). It activates PI3K/AKT, MAPK/ERK, and FAK/SRC signaling pathways, contributing to tumor invasion and stemness maintenance. Overexpressed in 60-80% of melanomas, triple-negative breast cancers, and glioblastomas, CSPG4 correlates with poor prognosis and therapeutic resistance. Emerging targeted therapies include CSPG4-specific monoclonal antibodies (9.2.27, TP41.2) in Phase I/II trials, chimeric antigen receptor (CAR) T-cell therapies for melanoma (NCT03434262), and antibody-drug conjugates leveraging its tumor-selective expression. Recent preclinical studies also implicate CSPG4 in multiple sclerosis via oligodendrocyte progenitor modulation.