Barrett's metaplasia as a paradigm for understanding the development of cancer

The conversion of one cell type to another is defined as metaplasia (or sometimes it is referred to as transdifferentiation or cellular reprogramming). Metaplasia is important clinically and may predispose to the development of cancer. Barrett's metaplasia is one such example and is the focus of the present review. Barrett's is a pathological condition in which the normal oesophageal stratified squamous epithelium is replaced by intestinal-type columnar epithelium and is associated with gastro-oesophageal reflux disease. The appearance of columnar epithelium in the oesophagus predisposes to the development of adenocarcinoma. Herein we review the latest evidence on the cellular origin of Barrett's metaplasia. Until recently it was thought that the cellular origin of the columnar epithelium was from a pre-existing cell within the oesophagus. However, recent evidence suggests that this may not be the case. Instead two recent publications indicate that the columnar cells may migrate from a site distal to the oesophagus. These new data contravene our current understanding of metaplasia and raise important questions about the cellular origin of cancer.