title: Heterogeneous expression and regulation of CD40 in human hepatocellular carcinoma.
abstract: OBJECTIVE
  CD40, a member of the tumour necrosis factor receptor family, plays a major role in adaptive immune responses and contributes to cancer surveillance. Conflicting results have been reported recently on the expression and function of CD40 in carcinomas. The aim of the present study was to investigate the role of CD40 in human hepatoma.
  
  
  METHODS
  CD40 expression was examined in hepatomas and derived cell lines by immunohistochemistry, flow cytometry and reverse transcriptase polymerase chain reaction. We investigated in hepatoma cell lines the regulation of CD40 by pro-inflammatory cytokines and the effects of its ligation with soluble CD40L on the expression of co-stimulatory and pro-apoptotic cell-surface molecules and survival.
  
  
  RESULTS
  CD40 was detected with a similar frequency of about 40% in hepatoma specimens and derived cell lines but not in normal hepatocytes. Tumour necrosis factor alpha and its combination with interferon gamma upregulated CD40 only in intrinsically positive cell lines. CD40 ligation had no effect on cell viability or surface expression of CD54, CD80, CD86 or CD95.
  
  
  CONCLUSIONS
  CD40 is expressed variably in human hepatoma and enhanced by distinct pro-inflammatory cytokines. The lack of detectable effects of CD40 ligation does not support a major role of this molecule in hepatocellular carcinoma biology.
authors.affiliation: Department of Gastroenterology and Hepatology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
authors.forename: Margareta
authors.initials: M
authors.lastname: Holub
authors.forename: Schaker M
authors.initials: SM
authors.lastname: Zakeri
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lichtenberger
authors.forename: Johannes
authors.initials: J
authors.lastname: Pammer
authors.forename: Pierre
authors.initials: P
authors.lastname: Paolini
authors.forename: Ludger
authors.initials: L
authors.lastname: Leifeld
authors.forename: Susanne
authors.initials: S
authors.lastname: Rockenschaub
authors.forename: Markus F
authors.initials: MF
authors.lastname: Wolschek
authors.forename: Günther
authors.initials: G
authors.lastname: Steger
authors.forename: Martin
authors.initials: M
authors.lastname: Willheim
authors.forename: Alfred
authors.initials: A
authors.lastname: Gangl
authors.forename: Walter
authors.initials: W
authors.lastname: Reinisch
mesh_terms: D000328:Adult; D000368:Aged; D019013:CD40 Antigens / Q000032:analysis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma