title: The role of GAGE cancer/testis antigen in metastasis: the jury is still out.
abstract: BACKGROUND
  GAGE cancer/testis antigens are frequently expressed in various types of malignancies and represent attractive targets for immunotherapy, however their role in cancer initiation and progression has remained elusive. GAGE proteins are expressed in normal cells during early development with migratory and invasive properties and were found to be upregulated in cancer cells with metastasizing potential in a gastric cancer model.
  
  
  METHODS
  We have addressed the direct role of GAGE proteins in supporting metastasis using an isogenic metastasis model of human cancer, consisting of 4 isogenic cell lines, which are equally tumorigenic in immunodeficient mice, but differ with their ability to generate metastases in the lungs and lymph nodes.
  
  
  RESULTS
  Although GAGE proteins were strongly upregulated in the highly metastatic clone (CL16) compared to non-metastatic (NM2C5), weakly metastatic (M4A4) and moderately metastatic clones (LM3), stable downregulation of GAGE expression did not affect the ability of CL16 cells to establish primary tumors and form metastasis in the lungs of immunodeficient mice.
  
  
  CONCLUSIONS
  These results suggest that GAGE proteins per se do not support metastasis and that further studies are needed to clarify the contribution of GAGE proteins to the metastatic potential of different types of cancer cells.
authors.affiliation: Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Winsloewparken 25, 3, Odense, DK-5000, Denmark. mgjerstorff@health.sdu.dk.
authors.forename: Morten Frier
authors.initials: MF
authors.lastname: Gjerstorff
authors.affiliation: Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Winsloewparken 25, 3, Odense, DK-5000, Denmark. mterp@health.sdu.dk.
authors.forename: Mikkel Green
authors.initials: MG
authors.lastname: Terp
authors.affiliation: Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Winsloewparken 25, 3, Odense, DK-5000, Denmark. malha10@student.sdu.dk.
authors.forename: Malene Bredahl
authors.initials: MB
authors.lastname: Hansen
authors.affiliation: Department of Cancer and Inflammation Research, Institute for Molecular Medicine, University of Southern Denmark, Winsloewparken 25, 3, Odense, DK-5000, Denmark. hditzel@health.sdu.dk.|Department of Oncology, Odense University Hospital, Sdr. Boulevard 29, Odense, DK-5000, Denmark. hditzel@health.sdu.dk.
authors.forename: Henrik Jørn
authors.initials: HJ
authors.lastname: Ditzel
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology; D051379:Mice; D005810:Multigene Family / Q000235:genetics; D009361:Neoplasm Invasiveness / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000951:Antigens, Neoplasm