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PLoS One. 2013 Dec 20;8(12):e82918. doi: 10.1371/journal.pone.0082918. eCollection 2013.

Identification of SLAMF3 (CD229) as an inhibitor of hepatocellular carcinoma cell proliferation and tumour progression.

Author information

  • 1INSERM UMR925 and EA 4666 UFR de Médecine, CAP-Santé (FED 4231), Université de Picardie Jules Verne, Amiens, France.
  • 2INSERM 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.
  • 3Service d'hématologie Clinique et de thérapie cellulaire Centre Hospitalier Universitaire sud, Amiens, France.
  • 4Service de Biochimie, Centre Hospitalier Universitaire sud, Amiens, France.
  • 5Service d'Anatomie Pathologique, Centre Hospitalier Universitaire sud, Amiens, France.
  • 6INSERM 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.
  • 7Service Hepato-Gastroenterologie, Centre Hospitalier Universitaire sud, Amiens, France.
  • 8Service de chirurgie digestive Centre Hospitalier Universitaire sud, Amiens, France.
  • 9INSERM 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.
  • 10IRNEM U768, Hôpital Necker enfants maladies, Paris, France.

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.

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