Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
Recent reports suggest that the East Asian liver fluke infection, caused by <i>Opisthorchis viverrini</i>, which is implicated in opisthorchiasis-associated cholangiocarcinoma, serves as a reservoir of <i>Helicobacter pylori</i>. The opisthorchiasis-affected cholangiocytes th...
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doaj-4a56a3cd2457496fb591fdf79963850c2020-11-25T04:11:31ZengMDPI AGPathogens2076-08172020-11-01997197110.3390/pathogens9110971Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human CholangiocytesPrissadee Thanaphongdecha0Shannon E. Karinshak1Wannaporn Ittiprasert2Victoria H. Mann3Yaovalux Chamgramol4Chawalit Pairojkul5James G. Fox6Sutas Suttiprapa7Banchob Sripa8Paul J. Brindley9Research 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, USAResearch 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, USAResearch 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, USAResearch 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, USADepartment of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDepartment of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandDivision of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USATropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandTropical Disease Research Laboratory, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, ThailandResearch 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, USARecent reports suggest that the East Asian liver fluke infection, caused by <i>Opisthorchis viverrini</i>, which is implicated in opisthorchiasis-associated cholangiocarcinoma, serves as a reservoir of <i>Helicobacter pylori</i>. 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, <i>Helicobacter pylori</i> strain NCTC 11637, and the congeneric bacillus, <i>Helicobacter</i><i> </i><i>bilis</i>. Exposure to increasing numbers of <i>H. pylori</i> 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 <i>H. pylori</i>, 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 <i>H.</i><i> </i><i>pylori</i><i> </i>bacilli per cell stimulated migration and invasion by the cholangiocytes. In addition, 10 bacilli of <i>H. pylori</i> stimulated contact-independent colony establishment in soft agar. These findings support the hypothesis that infection by <i>H.</i> <i>pylori</i><i> </i>contributes to the malignant transformation of the biliary epithelium.https://www.mdpi.com/2076-0817/9/11/971Helicobacter pyloricholangiocyteepithelial-to-mesenchymal transition |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Prissadee Thanaphongdecha Shannon E. Karinshak Wannaporn Ittiprasert Victoria H. Mann Yaovalux Chamgramol Chawalit Pairojkul James G. Fox Sutas Suttiprapa Banchob Sripa Paul J. Brindley |
spellingShingle |
Prissadee Thanaphongdecha Shannon E. Karinshak Wannaporn Ittiprasert Victoria H. Mann Yaovalux Chamgramol Chawalit Pairojkul James G. Fox Sutas Suttiprapa Banchob Sripa Paul J. Brindley Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes Pathogens Helicobacter pylori cholangiocyte epithelial-to-mesenchymal transition |
author_facet |
Prissadee Thanaphongdecha Shannon E. Karinshak Wannaporn Ittiprasert Victoria H. Mann Yaovalux Chamgramol Chawalit Pairojkul James G. Fox Sutas Suttiprapa Banchob Sripa Paul J. Brindley |
author_sort |
Prissadee Thanaphongdecha |
title |
Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes |
title_short |
Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes |
title_full |
Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes |
title_fullStr |
Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes |
title_full_unstemmed |
Infection with <i>Helicobacter pylori</i> Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes |
title_sort |
infection with <i>helicobacter pylori</i> induces epithelial to mesenchymal transition in human cholangiocytes |
publisher |
MDPI AG |
series |
Pathogens |
issn |
2076-0817 |
publishDate |
2020-11-01 |
description |
Recent reports suggest that the East Asian liver fluke infection, caused by <i>Opisthorchis viverrini</i>, which is implicated in opisthorchiasis-associated cholangiocarcinoma, serves as a reservoir of <i>Helicobacter pylori</i>. 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, <i>Helicobacter pylori</i> strain NCTC 11637, and the congeneric bacillus, <i>Helicobacter</i><i> </i><i>bilis</i>. Exposure to increasing numbers of <i>H. pylori</i> 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 <i>H. pylori</i>, 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 <i>H.</i><i> </i><i>pylori</i><i> </i>bacilli per cell stimulated migration and invasion by the cholangiocytes. In addition, 10 bacilli of <i>H. pylori</i> stimulated contact-independent colony establishment in soft agar. These findings support the hypothesis that infection by <i>H.</i> <i>pylori</i><i> </i>contributes to the malignant transformation of the biliary epithelium. |
topic |
Helicobacter pylori cholangiocyte epithelial-to-mesenchymal transition |
url |
https://www.mdpi.com/2076-0817/9/11/971 |
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