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

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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-affect...

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Main Authors: Thanaphongdecha, Prissadee, Karinshak, Shannon E, Ittiprasert, Wannaporn, Mann, Victoria H, Chamgramol, Yaovalux, Pairojkul, Chawalit, Fox, James G, Suttiprapa, Sutas, Sripa, Banchob, Brindley, Paul J
Format: Article
Language:English
Published: MDPI AG 2021
Online Access:https://hdl.handle.net/1721.1/135686
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author Thanaphongdecha, Prissadee
Karinshak, Shannon E
Ittiprasert, Wannaporn
Mann, Victoria H
Chamgramol, Yaovalux
Pairojkul, Chawalit
Fox, James G
Suttiprapa, Sutas
Sripa, Banchob
Brindley, Paul J
author_facet Thanaphongdecha, Prissadee
Karinshak, Shannon E
Ittiprasert, Wannaporn
Mann, Victoria H
Chamgramol, Yaovalux
Pairojkul, Chawalit
Fox, James G
Suttiprapa, Sutas
Sripa, Banchob
Brindley, Paul J
author_sort Thanaphongdecha, Prissadee
collection MIT
description © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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.
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spelling mit-1721.1/1356862021-10-28T03:13:25Z Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes Thanaphongdecha, Prissadee Karinshak, Shannon E Ittiprasert, Wannaporn Mann, Victoria H Chamgramol, Yaovalux Pairojkul, Chawalit Fox, James G Suttiprapa, Sutas Sripa, Banchob Brindley, Paul J © 2020 by the authors. Licensee MDPI, Basel, Switzerland. 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. 2021-10-27T20:28:47Z 2021-10-27T20:28:47Z 2020 2021-09-13T14:54:37Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135686 en 10.3390/PATHOGENS9110971 Pathogens Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf MDPI AG MDPI
spellingShingle Thanaphongdecha, Prissadee
Karinshak, Shannon E
Ittiprasert, Wannaporn
Mann, Victoria H
Chamgramol, Yaovalux
Pairojkul, Chawalit
Fox, James G
Suttiprapa, Sutas
Sripa, Banchob
Brindley, Paul J
Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title_full Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title_fullStr Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title_full_unstemmed Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title_short Infection with Helicobacter pylori Induces Epithelial to Mesenchymal Transition in Human Cholangiocytes
title_sort infection with helicobacter pylori induces epithelial to mesenchymal transition in human cholangiocytes
url https://hdl.handle.net/1721.1/135686
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