Heterogeneous expression and regulation of CD40 in human hepatocellular carcinoma.
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.
Holub
Margareta
M
Department of Gastroenterology and Hepatology, University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.
Zakeri
Schaker M
SM
Lichtenberger
Cornelia
C
Pammer
Johannes
J
Paolini
Pierre
P
Leifeld
Ludger
L
Rockenschaub
Susanne
S
Wolschek
Markus F
MF
Steger
Günther
G
Willheim
Martin
M
Gangl
Alfred
A
Reinisch
Walter
W
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
D019013:CD40 Antigens; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma