title: Gamma-smooth muscle actin expression is associated with epithelial-mesenchymal transition and stem-like properties in hepatocellular carcinoma.
abstract: OBJECTIVE
  The prognosis of hepatocellular carcinoma (HCC) is hampered by frequent tumour recurrence and metastases. Epithelial-Mesenchymal Transition (EMT) is now recognized as a key process in tumour invasion, metastasis and the generation of cancer initiating cells. The morphological identification of EMT in tumour samples from the expression of novel mesenchymal markers could provide relevant prognostic information and aid in understanding the metastatic process.
  
  
  METHODS
  The expression of Smooth Muscle Actins was studied using immunofluorescence and immunohistochemistry assays in cultured liver cells during an induced EMT process and in liver specimens from adult and paediatric HCC series.
  
  
  RESULTS
  We report here that in HCC cell lines treated with TGF-β and in HCC specimens, the expression of αSMA, a known mesenchymal marker of EMT, could never be detected. In addition, our in vitro studies identified the enteric form of SMA, γSMA, as being a marker of EMT. Moreover, this SMA isoform was expressed in 46% of 58 tumours from 42 adult HCC patients and in 90% of 16 tumours from 12 paediatric HCC patients. Interestingly, this expression was significantly correlated with poor tumour differentiation and progenitor cell features characterized by the expression of EpCAM and K19.
  
  
  CONCLUSIONS
  Taken together, our results support the conclusion that γSMA expression in HCC is strongly correlated with the EMT process, HCC aggressiveness and the identification of cancer stem cells. This correlation suggests that γSMA represents a novel and powerful marker to predict HCC progression.
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, France.
authors.forename: Nassima
authors.initials: N
authors.lastname: Benzoubir
authors.affiliation: AP-HP Hôpital Kremlin-Bicêtre, Service d'Anatomopathologie, Paris, France; DHU Hepatinov, Villejuif, France.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mussini
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Lejamtel
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, France.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dos Santos
authors.affiliation: AP-HP Hôpital Kremlin-Bicêtre, Service d'Anatomopathologie, Paris, France; DHU Hepatinov, Villejuif, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Guillaume
authors.affiliation: SFR André Lwoff, Villejuif, F-94800, France; DHU Hepatinov, Villejuif, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Desterke
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France; DHU Hepatinov, Villejuif, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; Institut Pasteur, Paris, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bréchot
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; AP-HP Hôpital Paul Brousse, Centre Hépatobiliaire, Villejuif, France; DHU Hepatinov, Villejuif, France.
authors.forename: Marie-Françoise
authors.initials: MF
authors.lastname: Bourgeade
authors.affiliation: Inserm, Unité 785, Villejuif, F-94800, France; Univ Paris-Sud, UMR-S 785, Villejuif, F-94800, France; AP-HP Hôpital Kremlin-Bicêtre, Service d'Anatomopathologie, Paris, France; DHU Hepatinov, Villejuif, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Guettier
mesh_terms: D000199:Actins / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015331:Cohort Studies; D000071858:Epithelial Cell Adhesion Molecule; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053539:Keratin-19 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D016017:Odds Ratio; D011379:Prognosis; D011994:Recombinant Proteins / Q000737:chemistry; D013234:Stem Cells / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: C579475:ACTG2 protein, human; D000199:Actins; D000951:Antigens, Neoplasm; D015415:Biomarkers; D015815:Cell Adhesion Molecules; C499379:EPCAM protein, human; D000071858:Epithelial Cell Adhesion Molecule; D053539:Keratin-19; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta