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Markers in breast cancer

Melanoma cell adhesion
molecule (MCAM)



Other name(s)

Melanoma-associated glycoprotein MUC18
MUC18
CD146
Mel-CAM


Molecular biology

Gene: MCAM spans approximately 14 kb and comprises 16 exons. The organization of the gene, which is related to that of the neural cell adhesion molecule N-CAM, shows a structure where each immunoglobulin-related domain is encoded by more than 1 exon. Recognition sequences for several transcription factors were observed, suggesting a role for this putative adhesion molecule in neural crest cells during embryonic development.
mRNA: size: ~3.6 kb.
Protein: a cell surface glycoprotein (113 kD), member of the immunoglobulin superfamily and homologous to several cell adhesion molecules. MCAM was associated with tumor progression and the development of metastasis in human malignant melanoma. MCAM sequence of 603 amino acids consists of a signal peptide, five immunoglobulin-like domains, a transmembrane region, and a short cytoplasmic tail. The highest sequence similarity is with a group of nervous system cell adhesion molecules, which includes neural cell adhesion molecule (N-CAM) (Lehmann J.M. et al., 1989).


Breast cancer

Cell lines:
- By flow cytometry analysis, MCAM was found to be expressed by SK-BR-3 (>50% positive cells), MDA-MB-435 (>10% positive cells), MCF-7 (1-10% positive cells), but not by BT-20 breast cancer cells (BCC). Thus, expression of MCAM could not be a common phenomenon of cultured epithelial tumor cells (Putz E. et al., 1999).

- The phenotypic characteristics of 2 BCC lines (BC-H1 and BC-K1) established from bone marrow of patients with breast cancer were studied by immunocytochemistry, flow cytometry, and RT-PCR. Both cell lines expressed E-cadherin, vimentin, cytokeratins (including component 18), alpha 5-, alpha V-, beta 1-, and beta 3- integrin subunits, ICAM-1, MCAM, LFA-3 (CD58), and CD44s (but not CD44v5, v6, v7/8). BC-H1 also expressed ErbB2 (not found in BC-K1), and MAGE-4 (but not MAGE-1, -2, -3/6, -12; BC-K1 was not tested). The expressed molecules might be potential candidates for novel therapeutic targets (Putz E. et al., 1999).

- Two BCC lines established from bone marrow of patients with breast cancer were found to express MCAM and ICAM-1 (Putz E. et al., 1999).

Tumors:
- The distribution and biological significance of MCAM was determined in normal, benign proliferative, and neoplastic breast ductal epithelium. MCAM expression was determined immunohistochemically in 14 of 14 (100%) normal breast epithelia and benign proliferative ductal epithelial lesions, whereas MCAM expression could 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 MCAM. Transfection of MCAM cDNA into breast carcinoma cells induced a more cohesive cell growth pattern and established smaller tumors in immunocompromised mice than mock transfectants. In conclusion, MCAM 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 MCAM expression in breast carcinoma might be an important step for tumor progression (Shih L.M. et al., 1997).

- 2 of 11 of infiltrating breast carcinomas, and 4 of 11 of germinomas were focally and weakly positive for MN-4, a mouse monoclonal antibody that specifically recognized a fixation-resistant epitope in the second extracellular (C2) domain of MCAM (Shih I.M. et al., 1998).



References

Lehmann J.M. et al. (1989) MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc. Natl. Acad. Sci. USA 86, 9891-9895.
Putz E. et al. (1999) Phenotypic characteristics of cell lines derived from disseminated cancer cells in bone marrow of patients with solid epithelial tumors: establishment of working models for human micrometastases. Cancer Res. 59, 241-248.
Sers C. et al. (1993) Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc. Natl. Acad. Sci. USA 90, 8514-8518.
Shih L.M. et al. (1997) The cell-cell adhesion receptor Mel-CAM acts as a tumor suppressor in breast carcinoma. Am. J. Pathol. 151, 745-751.
Shih I.M. et al. (1998) A new Mel-CAM (CD146)-specific monoclonal antibody, MN-4, on paraffin-embedded tissue. Mod. Pathol. 11, 1098-1106.



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