Host factors influence Barrett\u2019s carcinogenesis: findings from a mouse gastroduodenal reflux model

Shunpei Kanai,Hiroyuki Sugihara,Ken-Ichi Mukaisho,Naoko Taniura,Saori Yoshida

doi:10.1007/s10388-019-00660-5

Abstract

BackgroundRat gastroduodenal reflux models have been used for analyzing Barrett’s carcinogenesis. Mice seem to be more useful than rats for studies targeting genes.MethodsWe induced gastroduodenal contents reflux by esophagojejunostomy using C57BL/6J mice. Mice were divided into a standard diet and high-fat diet groups and kept for 60 weeks. Bile was sampled from the gallbladder to analyze bile acid fractions, and the esophagus was removed for a histological investigation. Human esophagogastric junction adenocarcinoma cells (OE19) were exposed to taurocholic acid (TCA), after which cell proliferative activity was measured. Rat esophageal cancer cell lines, ESCC-DR and ESCC-DRtca with higher malignant potential induced by continuous TCA exposure, were used to perform comprehensive genetic analysis (CGH).ResultsBarrett’s epithelium onset occurred in all mice, and no differences in histological changes were noted between the standard diet and high-fat diet groups. However, no development of adenocarcinoma was noted. Most of the mouse bile acid was taurine conjugates. In the experiment using OE-19 cells, TCA promotes cell proliferation in a dose-dependent manner. Array CGH analysis revealed a large number of chromosomal abnormalities in the ESCC-DR, in addition to genetic abnormalities such as in the UGT2B gene, the substrate of which is bile acid. TCA administration resulted in more chromosomal abnormalities being detected.ConclusionsWe showed the effects of TCA in cancer progression in vitro. However, Barrett’s adenocarcinoma onset rates differ between mice and rats despite undergoing similar reflux stimulation including taurine-conjugated bile acids being detected in mouse bile juice. These results suggest that host factors seem to influence Barrett’s carcinogenesis.

Highlights

Rat gastroduodenal reflux models have been used for analyzing Barrett’s carcinogenesis
In the mouse duodenal reflux model, the median weight was 27.2 g in the standard diet group and 33.2 g in the high-fat diet group, indicating that subjects were significantly heavier in the high-fat diet group (P value < 0.05)
Gastric intestinal metaplasia was reported to be positive for PDX-1, suggesting duodenal metaplasia rather than general intestinal metaplasia [15]

Summary

Introduction

Rat gastroduodenal reflux models have been used for analyzing Barrett’s carcinogenesis. Results Barrett’s epithelium onset occurred in all mice, and no differences in histological changes were noted between the standard diet and high-fat diet groups. Barrett’s adenocarcinoma onset rates differ between mice and rats despite undergoing similar reflux stimulation including taurine-conjugated bile acids being detected in mouse bile juice. These results suggest that host factors seem to influence Barrett’s carcinogenesis. We have reported that by providing such reflux model animals with a high-fat diet filled with beef tallow, the incidence of Barrett’s epithelium increased, resulting in a higher incidence of esophageal tumors [5]. We examined the histological changes in mice reflux modes using additional immunohistochemical stainings of CDX2, PDX1, and CK7, because CDX2 is a homeobox domain-containing transcription factor that is

Methods

Results

Conclusion