Bile Acid and Inflammation Activate Gastric Cardia Stem Cells in a Mouse Model of Barrett-like Metaplasia

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2012 Jan 24

PMID 22264787

Citations 250

Authors

Michael Quante

Govind Bhagat

Julian A Abrams

Frederic Marache

Pamela Good

Michele D Lee

Yoomi Lee

Richard Friedman

Samuel Asfaha

Zinaida Dubeykovskaya

Umar Mahmood

Jose-Luiz Figueiredo

Jan Kitajewski

Carrie Shawber

Charles J Lightdale

Anil K Rustgi

Timothy C Wang

Affiliations

Soon will be listed here.

Abstract

Esophageal adenocarcinoma (EAC) arises from Barrett esophagus (BE), intestinal-like columnar metaplasia linked to reflux esophagitis. In a transgenic mouse model of BE, esophageal overexpression of interleukin-1β phenocopies human pathology with evolution of esophagitis, Barrett-like metaplasia and EAC. Histopathology and gene signatures closely resembled human BE, with upregulation of TFF2, Bmp4, Cdx2, Notch1, and IL-6. The development of BE and EAC was accelerated by exposure to bile acids and/or nitrosamines, and inhibited by IL-6 deficiency. Lgr5(+) gastric cardia stem cells present in BE were able to lineage trace the early BE lesion. Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1β-IL-6 signaling cascade and Dll1-dependent Notch signaling.

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