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PMID: 9284823 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The American journal of pathology ·Vol. 151 ·No. 3 ·1997-09-00 ·Pages 745-51

Shih LM, Hsu MY, Palazzo JP, Herlyn M

Abstract

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.

MeSH Terms
Animals Antibodies, Monoclonal Antigens, CD Blotting, Western Breast/metabolism Breast Diseases/metabolism Breast Neoplasms/genetics,metabolism CD146 Antigen Cell Adhesion/genetics Cells, Cultured Epithelium/metabolism Female Gene Expression Humans Immunohistochemistry Mammary Neoplasms, Experimental/genetics,pathology Membrane Glycoproteins/genetics,metabolism Mice Mice, SCID Neoplasm Transplantation Neural Cell Adhesion Molecules Transfection Tumor Cells, Cultured
Chemicals
Antibodies, Monoclonal Antigens, CD CD146 Antigen MCAM protein, human Mcam protein, mouse Membrane Glycoproteins Neural Cell Adhesion Molecules
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Shih L M
Wistar Institute, Philadelphia, PA 19104-4268, USA.
Hsu M Y
Palazzo J P
Herlyn M
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1997-09-00
Pages
745-51
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1857834
Subset
IM
Grants
NCI NIH HHS · CA-25874 · United States
NCI NIH HHS · CA-47159 · United States
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