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Lookup NU author(s): Dr Ute JungwirthORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The AuthorsBarrett's oesophagus (BO) is a pathological condition in which the squamous epithelium of the distal oesophagus is replaced by an intestinal-like columnar epithelium originating from the gastric cardia. Several somatic mutations contribute to the intestinal-like metaplasia. Once these have occurred in a single cell, it will be unable to expand further unless the altered cell can colonise the surrounding squamous epithelium of the oesophagus. The mechanisms by which this happens are still unknown. Here we have established an in vitro system for examining the competitive behaviour of two epithelia. We find that when an oesophageal epithelium model (Het1A cells) is confronted by an intestinal epithelium model (Caco-2 cells), the intestinal cells expand into the oesophageal domain. In this case the boundary involves overgrowth by the Caco-2 cells and the formation of isolated colonies. Two key transcription factors, normally involved in intestinal development, HNF4α and CDX2, are both expressed in BO. We examined the competitive ability of Het1A cells stably expressing HNF4α or CDX2 and placed in confrontation with unmodified Het1A cells. The key result is that stable expression of HNF4α, but not CDX2, increased the ability of the cells to migrate and push into the unmodified Het1A domain. In this situation the boundary between the cell types is a sharp one, as is normally seen in BO. The experiments were conducted using a variety of extracellular substrates, which all tended to increase the cell migration compared to uncoated plastic. These data provide evidence that HNF4α expression could have a potential role in the competitive spread of BO into the oesophagus as HNF4α increases the ability of cells to invade into the adjacent stratified squamous epithelium, thus enabling a single mutant cell eventually to generate a macroscopic patch of metaplasia.
Author(s): Grimaldos Rodriguez C, Rimmer EF, Colleypriest B, Tosh D, Slack JMW, Jungwirth U
Publication type: Article
Publication status: Published
Journal: Differentiation
Year: 2023
Volume: 134
Pages: 1-10
Print publication date: 01/11/2023
Online publication date: 23/08/2023
Acceptance date: 22/08/2023
Date deposited: 12/02/2024
ISSN (print): 0301-4681
ISSN (electronic): 1432-0436
Publisher: Elsevier Ltd
URL: https://doi.org/10.1016/j.diff.2023.08.003
DOI: 10.1016/j.diff.2023.08.003
PubMed id: 37690144
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