Abstract
Recent reports suggest that the East Asian liver fluke infection, caused by Opisthorchis viverrini, which is implicated in opisthorchiasis-associated cholangiocarcinoma, serves as a reservoir of Helicobacter pylori. The opisthorchiasis-affected cholangiocytes that line the intrahepatic biliary tract are considered to be the cell of origin of this malignancy. Here, we investigated interactions in vitro among human cholangiocytes, Helicobacter pylori strain NCTC 11637, and the congeneric bacillus, Helicobacter bilis. Exposure to increasing numbers of H. pylori at 0, 1, 10, 100 bacilli per cholangiocyte of the H69 cell line induced phenotypic changes including the profusion of thread-like filopodia and a loss of cell-cell contact, in a dose-dependent fashion. In parallel, following exposure to H. pylori, changes were evident in levels of mRNA expression of epithelial to mesenchymal transition (EMT)-encoding factors including snail, slug, vimentin, matrix metalloprotease, zinc finger E-box-binding homeobox, and the cancer stem cell marker CD44. Analysis to quantify cellular proliferation, migration, and invasion in real-time by both H69 cholangiocytes and CC-LP-1 line of cholangiocarcinoma cells using the xCELLigence approach and Matrigel matrix revealed that exposure to ≥10 H. pylori bacilli per cell stimulated migration and invasion by the cholangiocytes. In addition, 10 bacilli of H. pylori stimulated contact-independent colony establishment in soft agar. These findings support the hypothesis that infection by H. pylori contributes to the malignant transformation of the biliary epithelium.
Highlights
There is increasing evidence that the East Asian liver fluke Opisthorchis viverrini may serve as a reservoir of Helicobacter, which, in turn, implicates Helicobacter in the pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA) [1,2,3,4,5]
Lesions ascribed to liver fluke infection including cholangitis, biliary hyperplasia and metaplasia, periductal fibrosis, and CCA may be, in part, Helicobacter-associated hepatobiliary disease
H69 were directly exposed to increasing number of H. pylori strain NCTC 11637 at 0, 10, and 100 bacilli per cholangiocyte in 6-well plates
Summary
There is increasing evidence that the East Asian liver fluke Opisthorchis viverrini may serve as a reservoir of Helicobacter, which, in turn, implicates Helicobacter in the pathogenesis of opisthorchiasis-associated cholangiocarcinoma (CCA) [1,2,3,4,5]. The International Agency for Research on Cancer of the World Health Organization categorizes infection with the food-borne liver flukes, O. viverrini and Clonorchis sinensis, as Group 1 carcinogens [6]. Given the elevated prevalence of CCA in this region, where infection with liver fluke prevails, and given the evidence of linkages between infection by Helicobacter during opisthorchiasis, these two biological carcinogens together may orchestrate the pathogenesis of opisthorchiasis and bile duct cancer. It has been hypothesized that the association of Helicobacter and its virulence factors, including during opisthorchiasis, underlies much biliary tract disease including CCA in liver fluke-endemic regions [10]. Lesions ascribed to liver fluke infection including cholangitis, biliary hyperplasia and metaplasia, periductal fibrosis, and CCA may be, in part, Helicobacter-associated hepatobiliary disease
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
