title: METCAM/MUC18 is a novel tumor and metastasis suppressor for the human ovarian cancer SKOV3 cells.
abstract: 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.
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. guangj.wu@gmail.com.|Department of Bioscience Technology, Chung Yuan Christian University, Chung Li, 32023, Taiwan. guangj.wu@gmail.com.|Center for Biomedical Technology, Chung Yuan Christian University, Chung Li, 32023, Taiwan. guangj.wu@gmail.com.
authors.forename: Guang-Jer
authors.initials: GJ
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA, 30322, USA. guofangz@yahoo.com.|Present Address: Department of Hepatobiliary Surgery, Institute of Plastic Surgery, and Laboratory of Regenerative Medicine, Affiliated Hospital of Guangdong Medical College, Zhanjiang, 542001, China. guofangz@yahoo.com.
authors.forename: Guo-fang
authors.initials: GF
authors.lastname: Zeng
mesh_terms: D000818:Animals; D051929:CD146 Antigen / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*
chemical_list: D051929:CD146 Antigen; C497902:MCAM protein, human