In vivo expression of soluble Fas and FAP-1: possible mechanisms of Fas resistance in human hepatoblastomas

Abstract

Many tumour cells express both Fas and its ligand (FasL) on their surface and it has remained a mystery why such cells do not simply kill themselves. It remains to be determined whether Fas and FasL are expressed in human hepatoblastomas and if so, what is responsible for the possible Fas resistance of these tumours. In this study, the expression of Fas and FasL was examined in 23 cases of human hepatoblastoma by immunohistochemical staining. To elucidate possible Fas resistance in hepatoblastomas, Fas-resistance pathways including the expression of bcl-2 and Fas-associated phosphatase-1 (FAP-1), and the expression of soluble Fas (sFas) mRNA, were analysed by immunohistochemistry and in situ reverse transcription-polymerase chain reaction (in situ RT-PCR). Fas gene mutation in the death domain was also examined. Fas and FasL were expressed in all hepatoblastomas analysed. Twenty (87 per cent) and 18 (78 per cent) cases of hepatoblastoma were positive for sFas mRNA and FAP-1, respectively, but none of the hepatoblastomas expressed bcl-2. Mutation in the death domain of the Fas gene was not found in hepatoblastomas. Taken together, these findings demonstrated that Fas, a death receptor, and its ligand are co-expressed in hepatoblastomas in vivo, but some inhibitors of Fas-mediated apoptosis are also expressed in these tumours. These results suggest that it is probably due to the action of inhibitory molecules of the Fas pathway that the tumour cells of hepatoblastomas do not kill themselves in an autocrine-driven cycle and that in this manner hepatoblastomas avoid apoptosis.