title: Identification of SLAMF3 (CD229) as an inhibitor of hepatocellular carcinoma cell proliferation and tumour progression.
abstract: Although hepatocellular carcinoma (HCC) is one of the most common malignancies and constitutes the third leading cause of cancer-related deaths, the underlying molecular mechanisms are not fully understood. In the present study, we demonstrate for the first time that hepatocytes express signalling lymphocytic activation molecule family member 3 (SLAMF3/CD229) but not other SLAMF members. We provide evidence to show that SLAMF3 is involved in the control of hepatocyte proliferation and in hepatocellular carcinogenesis. SLAMF3 expression is significantly lower in primary human HCC samples and HCC cell lines than in human healthy primary hepatocytes. In HCC cell lines, the restoration of high levels of SLAMF3 expression inhibited cell proliferation and migration and enhanced apoptosis. Furthermore, SLAMF3 expression was associated with inhibition of HCC xenograft progression in the nude mouse model. The restoration of SLAMF3 expression levels also decreased the phosphorylation of MAPK ERK1/2, JNK and mTOR. In samples from resected HCC patients, SLAMF3 expression levels were significantly lower in tumorous tissues than in peritumoral tissues. Our results identify SLAMF3 as a specific marker of normal hepatocytes and provide evidence for its potential role in the control of proliferation of HCC cells.
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Marcq
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Rémy
authors.initials: R
authors.lastname: Nyga
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France ; INSERM U1053, Laboratoire de Physiologie du Cancer du Foie, Université Bordeaux Segalen, 146, rue Léo Saignat, Bordeaux, France.
authors.forename: Flora
authors.initials: F
authors.lastname: Cartier
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Rabbind Singh
authors.initials: RS
authors.lastname: Amrathlal
authors.affiliation: Service d'hématologie Clinique et de thérapie cellulaire Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Christèle
authors.initials: C
authors.lastname: Ossart
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Hakim
authors.initials: H
authors.lastname: Ouled-Haddou
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Hussein
authors.initials: H
authors.lastname: Ghamlouch
authors.affiliation: Service de Biochimie, Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Galmiche
authors.affiliation: Service d'Anatomie Pathologique, Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Chatelain
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Luciane
authors.initials: L
authors.lastname: Lamotte
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Debuysscher
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France ; Service d'Immunologie, Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Fuentes
authors.affiliation: Service Hepato-Gastroenterologie, Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Nguyen-Khac
authors.affiliation: Service de chirurgie digestive Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Regimbeau
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France ; Service d'hématologie Clinique et de thérapie cellulaire Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Marolleau
authors.affiliation: IRNEM U768, Hôpital Necker enfants maladies, Paris, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Latour
authors.affiliation: INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France ; Service d'hématologie Clinique et de thérapie cellulaire Centre Hospitalier Universitaire sud, Amiens, France.
authors.forename: Hicham
authors.initials: H
authors.lastname: Bouhlal
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007279:Injections, Subcutaneous; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009368:Neoplasm Transplantation; D015398:Signal Transduction; D000071176:Signaling Lymphocytic Activation Molecule Family; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C430423:LY9 protein, human; C498972:Ly9 protein, mouse; D000071176:Signaling Lymphocytic Activation Molecule Family; C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048670:MAP Kinase Kinase 4