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The altered expression of cell adhesion molecules (CAMs) correlates with the malignant progression of many epithelial tumors. MUC18/CD146/A32/MelCAM/S-endo 1, a CAM in the immunoglobulin gene superfamily, is an integral membrane glycoprotein. MUC18 is not a mucin, resulting from its misleading nomenclature by the original discoverer. We re-named it as METCAM (metastasis-regulating CAM), based on its very interesting biological roles in tumor formation and metastasis of many epithelial tumors. Initial findings show that METCAM/MUC18 expression has a positive effect (as a tumor and metastasis promoter) on the progression of breast cancer, most melanoma cell lines, nasopharyngeal carcinoma (NPC) type II, and prostate cancer. Later research results show that METCAM/ MUC18 expression has a negative effect (as a tumor suppressor and metastasis suppressor) on the progression of ovarian cancer, one mouse melanoma cell line, and nasopharyngeal carcinoma type I, and perhaps hemangioma. Since the above dual function of METCAM/ MUC18 occurs only in different cell lines from the same cancer type or in those from different cancer types, we suggest that the different effect of METCAM/MUC18 on tumor formation and metastasis of different cancer cell line may be due to different intrinsic properties (co-factors) in each cancer cell line that modify the biological functions of METCAM/ MUC18 in the intrinsic properties of tumor cells and their interactions with the tumor microenvironment. This chapter will review the published work and present some possible mechanisms for the METCAM/MUC18-mediated cancer progression for future studies.

Dual Role of METCAM/MUC18 Expression in the Progression of Cancer Cells