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.
Part of the book: Gene Expression and Regulation in Mammalian Cells
METCAM/MUC18, a component of cellular membrane, is a cell adhesion molecule (CAM) in the Ig-like gene super-family. It is capable of carrying out general functions of CAMs, such as performing intercellular interactions and interaction of cell with extracellular matrix in tumor microenvironment, interacting with various signaling pathways, and regulating social behaviors of cells. METCAM/MUC18 plays the tumor suppressor function in some cancers, such as colorectal cancer, nasopharyngeal carcinoma type I, one mouse melanoma subline K1735-9, ovarian cancer, pancreatic cancer, prostate cancer PC-3 cell line, and perhaps hemangioma. Possible mechanism in the METCAM/MUC18-mediated tumor suppression is proposed. By taking advantage of the tumor suppressor function of METCAM/MUC18, recombinant METCAM/MUC18 proteins and other derived products may be used as therapeutic agents to treat these cancers.
Part of the book: Genes and Cancer
In addition to oncogenes and tumor suppressor genes, cell adhesion molecules (CAMs) also significantly contribute to tumor progression and metastasis. For the past two decades, we have demonstrated that METCAM/MUC18, a cell adhesion molecule in the immunoglobulin-like gene superfamily, orchestrates complex interactions of tumor cells with various stromal cells in the tumor microenvironment, resulting in augmentation or reduction of the metastatic potential of carcinoma cells. Here we show that METCAM/MUC18 plays a positive role in the tumor progression and metastasis in most human cancers, such as breast cancer, human melanoma and most mouse melanoma, nasopharyngeal carcinoma type III, prostate cancer LNCaP and DU145 cell lines, and perhaps angiosarcoma, gastric cancer, glioma, hepatocellular carcinoma, non-small cell lung adenocarcinoma, small cell lung cancer (SCLC), osteosarcoma, and human and mouse pancreatic cancer. Possible mechanisms in the METCAM/MUC18-mediated tumor progression and metastasis are proposed. Anti-METCAM/MUC18 antibodies and siRNAs may be used as therapeutic agents to treat these cancers.
Part of the book: Tumor Progression and Metastasis