The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma

Mel-CAM (MUC18 or CD146) is a cell adhesion molecule sharing sequence homology with members of the immunoglobulin gene superfamily. Mel-CAM was originally described as a marker associated with invasion and metastasis in melanoma. We determined here the distribution and biological significance of Mel-CAM in normal, benign proliferative, and neoplastic breast ductal epithelium. Using a Mel-CAM-specific monoclonal antibody, we immunohistochemically demonstrate Mel-CAM expression in 14 of 14 (100%) normal breast epithelia and benign proliferative ductal epithelial lesions, whereas Mel-CAM expression can only be locally detected in 12 of 72 (17%) breast carcinomas. Solid-phase cell adhesion assay revealed that breast carcinoma cells in culture express the ligand for Mel-CAM. Transfection of Mel-CAM cDNA into breast carcinoma cells induces a more cohesive cell growth pattern and establishes smaller minors in immunocompromised mice than mock transfectants. In conclusion, Mel-CAM is distributed throughout normal and benign proliferative mammary ductal epithelium, but it is frequently lost in carcinomas; it functions as a heterophilic cell-cell adhesion molecule in breast epithelium, and loss of Mel-CAM expression in breast carcinoma may be an important step for tumor progression.