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Open AccessArticle

Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes

Research Center for Neglected Tropical Diseases of Poverty, Department of Microbiology, Immunology and Tropical Medicine, School of Medicine & Health Sciences, The George Washington University, Washington, DC 20037, USA
Tropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand
Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
Authors to whom correspondence should be addressed.
Pathogens 2020, 9(11), 971;
Received: 4 October 2020 / Revised: 14 November 2020 / Accepted: 18 November 2020 / Published: 21 November 2020
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. View Full-Text
Keywords: Helicobacter pylori; cholangiocyte; epithelial-to-mesenchymal transition Helicobacter pylori; cholangiocyte; epithelial-to-mesenchymal transition
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Thanaphongdecha, P.; Karinshak, S.E.; Ittiprasert, W.; Mann, V.H.; Chamgramol, Y.; Pairojkul, C.; Fox, J.G.; Suttiprapa, S.; Sripa, B.; Brindley, P.J. Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes. Pathogens 2020, 9, 971.

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