Mechanisms of Barrett's oesophagus: intestinal differentiation, stem cells, and tissue models.
Barrett's oesophagus (BE) is defined as any metaplastic columnar epithelium in the distal oesophagus which replaces normal squamous epithelium and which predisposes to cancer development. It is this second requirement, the predisposition to cancer, which makes this condition both clinically highly relevant and an important area for ongoing research. While BE has been defined pathologically since the 1950's (Allison and Johnstone, Thorax 1955), and identified as a risk factor for esophageal adenocarcinoma since the 1970's (Naef A.P., et al J Thorac Cardiovasc Surg. 1975), our understanding of the molecular events giving rise to this condition remains limited. Herein we will examine what is known about the intestinal features of BE and how well it recapitulates the intestinal epithelium, including stem identity and function. Finally, we will explore laboratory models of this condition presently in use and under development, to identify new insights they may provide into this important clinical condition.
Division of Gastroenterology, 421 Curie Boulevard, 956 Biomedical Research Building, Philadelphia, PA, 19104, USA. Electronic address: nakagawh@mail.med.upenn.edu.
Hiroshi
H
Nakagawa
Division of Gastroenterology, 421 Curie Boulevard, 956 Biomedical Research Building, Philadelphia, PA, 19104, USA. Electronic address: whelank@mail.med.upenn.edu.
Kelly
K
Whelan
Division of Gastroenterology, 421 Curie Boulevard, 956 Biomedical Research Building, Philadelphia, PA, 19104, USA. Electronic address: lynchj@mail.med.upenn.edu.
John P
JP
Lynch
D000230:Adenocarcinoma / Q000209:etiology / Q000473:pathology; D000818:Animals; D001471:Barrett Esophagus / Q000209:etiology* / Q000473:pathology*; D004938:Esophageal Neoplasms / Q000209:etiology / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000473:pathology; D011230:Precancerous Conditions / Q000209:etiology* / Q000473:pathology*; D012307:Risk Factors; D013234:Stem Cells / Q000473:pathology
(3-10) gastroesophageal reflux disease (GERD); BMP4; Barrett's oesophagus (BE); Cdx2; Esophageal adenocarcinoma (EAC); Hedgehog; Human 3D organotypic model systems (OTC); Multi-layered epithelium (MLE); Sox2; Tissue engineering