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 focally 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 tumors 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.
Shih
L M
LM
Wistar Institute, Philadelphia, PA 19104-4268, USA.
Hsu
M Y
MY
Palazzo
J P
JP
Herlyn
M
M
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015153:Blotting, Western; D001940:Breast / Q000378:metabolism*; D001941:Breast Diseases / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D051929:CD146 Antigen; D002448:Cell Adhesion / Q000235:genetics; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D019006:Neural Cell Adhesion Molecules; D014162:Transfection; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D051929:CD146 Antigen; C497902:MCAM protein, human; C497903:Mcam protein, mouse; D008562:Membrane Glycoproteins; D019006:Neural Cell Adhesion Molecules