MCAM (melanoma cell adhesion molecule) is a cell adhesion protein with critical roles in vascular biology and cancer progression. Primarily expressed on endothelial cells and fibroblasts 1, MCAM mediates cell-cell adhesion at vascular junctions and functions as a surface receptor triggering tyrosine phosphorylation and calcium signaling. In cancer contexts, MCAM+ cancer-associated fibroblasts (CAFs) significantly influence tumor microenvironment composition and immune regulation. In colorectal cancer, MCAM+ CAFs derived from pericryptal fibroblasts promote tumor growth through IL-1R1-dependent NF-κB signaling that recruits tumor-associated macrophages via IL-34/CCL8 axes 2. Similarly, in endometrial cancer, CD146+ CAFs drive angiogenesis and vasculogenic mimicry through IL-10-mediated JAK1/STAT3 signaling 3. MCAM also marks progenitor cells in meniscus tissue and contributes to immunopathology—MCAM+ T cells demonstrate enhanced IL-17 production and endothelial-binding capacity, accumulating in autoimmune disease sites 4. Clinically, soluble MCAM in blood serves as a prognostic biomarker for liver cirrhosis and hepatocellular carcinoma progression 1, while MCAM expression on solid tumors enables targeted immunotherapy approaches 5. High MCAM expression in various cancers correlates inversely with patient survival, establishing it as both a therapeutic target and prognostic indicator.