title: Melanoma-expressed CD70 is involved in invasion and metastasis.
abstract: BACKGROUND
  CD70 is a costimulatory molecule of the tumour necrosis factor family expressed in activated immune cells and some solid tumours. In lymphocytes CD70 triggers T cell-mediated cytotoxicity and mitogen-activated protein kinase phosphorylation.
  
  
  METHODS
  We evaluated the expression of CD70 in biopsies and melanoma cell lines. Using melanoma cell lines positive or not for CD70, we analysed CD70 function on melanoma progression.
  
  
  RESULTS
  We report CD70 expression in human melanoma cell lines and tumour cells from melanoma biopsies. This expression was observed in 95% of primary melanomas but only 37% of metastases. Both monomeric and trimeric forms of CD70 were detected in tumour cell membrane fractions, whereas cytoplasmic fractions contained almost exclusively monomeric CD70. In vitro and in vivo experiments demonstrated that CD70 expression inhibited melanoma cell migration, invasion and pulmonary metastasis implantation independently of the tumour immune microenvironment. Increasing the levels of the trimeric form of CD70 through monoclonal antibody binding led to an increase in CD70+ melanoma cell invasiveness through MAPK pathway activation, RhoE overexpression, ROCK1 and MYPT1 phosphorylation decrease, and stress fibres and focal adhesions disappearance.
  
  
  CONCLUSIONS
  Our results describe a new non-immunological function of melanoma-expressed CD70, which involves melanoma invasiveness through MAPK pathway, RhoE and cytoskeletal modulation.
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Université Paul Sabatier, F-31062 Toulouse, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Pich
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Université Paul Sabatier, F-31062 Toulouse, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Sarrabayrouse
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Université Paul Sabatier, F-31062 Toulouse, France.
authors.forename: Iotefa
authors.initials: I
authors.lastname: Teiti
authors.affiliation: Université Paul Sabatier, F-31062 Toulouse, France.|ITAV, USR 3505, 1 Place Potier, F-31106 Toulouse, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Mariamé
authors.affiliation: Service d'anatomo-Pathologie, Institut Universitaire du Cancer - IUCT, F-31059 Toulouse, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Rochaix
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Service d'anatomo-Pathologie, Institut Universitaire du Cancer - IUCT, F-31059 Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Université Paul Sabatier, F-31062 Toulouse, France.|Service d'anatomo-Pathologie, Institut Universitaire du Cancer - IUCT, F-31059 Toulouse, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Favre
authors.affiliation: Service d'anatomo-Pathologie, Institut Universitaire du Cancer - IUCT, F-31059 Toulouse, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Maisongrosse
authors.affiliation: Unité INSERM UMR 1037, CRCT, F-31037 Toulouse, France.|Université Paul Sabatier, F-31062 Toulouse, France.
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Tilkin-Mariamé
mesh_terms: D000818:Animals; D053282:CD27 Ligand / Q000032:analysis / Q000502:physiology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D003599:Cytoskeleton / Q000502:physiology; D005260:Female; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D008545:Melanoma / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D020741:rho GTP-Binding Proteins / Q000502:physiology; D054460:rho-Associated Kinases / Q000502:physiology
chemical_list: D053282:CD27 Ligand; C505771:CD70 protein, human; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases; C508705:RND3 protein, human; D020741:rho GTP-Binding Proteins