title: Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors: Bioengineering College, Chongqing University, Chongqing 400044, China.
authors: Guo-Fang
authors: GF
authors: Zeng
authors: Shao-Xi
authors: SX
authors: Cai
authors: Guang-Jer
authors: GJ
authors: Wu
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D051929:CD146 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018929:Cell Culture Techniques; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D018450:Disease Progression; D005260:Female; D006801:Humans; D009361:Neoplasm Invasiveness / Q000235:genetics; D009362:Neoplasm Metastasis; D019076:Transgenes / Q000235:genetics; D014410:Tumor Stem Cell Assay
chemical_list: D019138:Antibodies, Blocking; D051929:CD146 Antigen; C497902:MCAM protein, human