Melanoma cell adhesion molecule (MCAM) (MCAM)

Melanoma cell adhesion molecule (MCAM), also known as CD146, is a transmembrane glycoprotein belonging to the immunoglobulin superfamily that functions as a calcium-independent cell adhesion molecule. While it is primarily expressed on the vascular endothelium and smooth muscle cells, a soluble form (sMCAM or sCD146) is generated through proteolytic shedding of the membrane-bound protein by metalloproteinases such as ADAM10 and ADAM17 (UniProt P43121; Bardin et al., 2001). sMCAM acts as a potent pro-angiogenic factor by binding to and activating VEGFR2, and it plays a critical role in the transmigration of inflammatory cells, particularly Th17 cells, across the blood-brain barrier in neuroinflammatory diseases (PubMed: 25548234). In oncology, elevated levels of sMCAM in the serum are strongly correlated with advanced tumor stage, increased metastatic potential, and poor clinical outcomes in cancers such as melanoma and breast carcinoma (PubMed: 14710230). Therapeutic development has focused on monoclonal antibodies like ABX-MA1 and PRX003, which target MCAM to inhibit pathological angiogenesis and reduce the infiltration of pathogenic immune cells into the central nervous system.

Other names

CD146MUC18Soluble CD146 (sCD146)Soluble Melanoma cell adhesion molecule (sMCAM)Cell surface glycoprotein P1H12MET-CAMA32 antigen

Monoclonal antibodies bind to the extracellular domain of MCAM or its soluble form (sMCAM) to block interactions with ligands such as laminin-411 or receptors like VEGFR2, thereby inhibiting tumor angiogenesis, cell metastasis, and the extravasation of inflammatory T-cells into tissues.