THE CELL-CELL ADHESION RECEPTOR MEL-CAM ACTS AS A TUMOR-SUPPRESSOR INBREAST-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 meta stasis in melanoma. We determined here the distribution and biological significance of Mel-CAM in normal, benign proliferative, and neoplast ic breast ductal epithelium. Using a Mel-CAM-specific monoclonal antib ody, we immunohistochemically demonstrate Mel-CAM expression in 14 of 14 (100%) normal breast epithelia and benign proliferative ductal epit helial lesions, whereas Mel-CAM expression can only be focally detecte d in 12 of 72 (17%) breast carcinomas, Solid-phase cell adhesion assay revealed that breast carcinoma cells in culture express the Ligand fo r Mel-CAM. Transfection of Mel-CAM cDNA into breast carcinoma cells in duces a more cohesive cell growth pattern and establishes smaller tumo rs in immunocompromised mice than mock transfectants, In conclusion, M el-CAM is distributed throughout normal and benign proliferative mamma ry ductal epithelium, but it is frequently lost in carcinomas; it func tions as a heterophilic cell-cell adhesion molecule In breast epitheli um, and loss of Mel-CAM expression in breast carcinoma may be an impor tant step for tumor progression.