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Background: Increased expression of METCAM/MUC18, a trans-membrane cell adhesion molecule in the Ig-like gene superfamily, has been associated with the malignant progression of epithelial ovarian carcinomas. To investigate if this is a fortuitous correlation or if METCAM/MUC18 actually plays a role in the progression of the cancer, we tested effects of enforced expression of METCAM/MUC18 on in vitro behaviors, in vivo tumorigenesis, and in vivo malignant progression of human ovarian cancer SK-OV-3 cells, which minimally expressed this protein., Methods: For in vitro and in vivo tests, we transfected human METCAM/MUC18 cDNA gene into SK-OV-3 cells in a mammalian expression vector pcDNA3.1+ and obtained G418-resistant (G418(R)) clones, which expressed various levels of human METCAM/MUC18. To mimic physiological situations, we used pooled METCAM/MUC18-expressing and control (vector) clones for testing effects of human METCAM/MUC18 over-expression on in vitro motility and invasiveness, and on in vivo tumor formation and metastasis in female athymic nude mice. Effects of METCAM/MUC18 on the expression of various downstream key factors related to tumorigenesis were also evaluated by Western blot analyses., Results: The over-expression of METCAM/MUC18 inhibited in vitro motility and invasiveness of SK-OV-3 cells. SK-OV-3 cells of the control (vector) clone (3D), which did not express human METCAM/MUC18, supported the formation of a solid tumor after SC injection of the cells at dorsal or ventral sites and also formation of solid tumor and ascites after IP injection in the intraperitoneal cavity of nude mice. In contrast, SK-OV-3 cells from the METCAM/MUC18-expressing clone (2D), which expressed a high level of METCAM/MUC18, did not support the formation of a solid tumor at SC sites, or formation of ascites in the intraperitoneal cavity of nude mice. Expression levels of downstream key factors, which may affect tumor proliferation and angiogenesis, were reduced in tumors induced by the METCAM/MUC18-expressing clone (2D)., Conclusions: We conclude that increased human METCAM/MUC18 expression in ovarian cancer SK-OV-3 cells suppressed tumorigenesis and ascites formation in nude mice, suggesting that human METCAM/MUC18 plays a suppressor role in the progression of ovarian cancer, perhaps by reducing proliferation and angiogenesis.

Background: Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells., Methods: Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein.MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody., Results: In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture., Conclusion: These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.