Possible involvement of hepatic progenitor cells in hepatocarcinogenesis

Abstract

[Background] There is increasing evidence that progenitor cells might participate in tumorigenesis, although involvement of progenitor cells in hepatocarcinogenesis remain unknown. In this study, we examined expression of progenitor cell markers in hepatocellular carcinoma (HCC) and its precursor lesions. [Methods] We used paraffin embedded and frozen sections of classical HCC (10 cases), early HCC (10 cases), and dysplastic nodule (DN) (10 cases). We performed immunostaining of ABCG2 and type 3 muscarinic acetylcholine receptor (M3R), both of which were new markers for hepatic progenitor cells. We also examined expression of ABCG2 and M3R in HCC culture cells (HepG2, HuH28, PLC5) by RT-PCR, Western blot, and immunostaining. [Results] ABCG2 was expressed in canalicular membrane of small dysplastic cells around portal tracts in DN and early HCC. In classical HCCs, ABCG2 expression was observed in cytoplasm or lateral membrane in addition to canalicular membrane. M3R was also expressed in small dysplastic cells around portal tracts in DN and early HCC. ABCG2 and M3R expressions in cultured HCC cells were confirmed at mRNA and protein levels. Furthermore, immunostaining revealed a group of ABCG2/M3R double positive cells in a whole cultured HCC cells. [Discussion] This study revealed that HCC and precursor lesions contained dysplastic cells expressing progenitor cell markers. It is interesting that these positive cells were observed around portal tracts, where hepatic progenitor cells (Hering's canals or bile ductules) exist in non-neoplastic liver. This study suggests possible involvement of hepatic progenitor cells in human hepatocarcinogenesis.