Continual self-renewal of the gastric epithelium by cell differentiation. Implications for carcinogenesis

Background. The gastric mucosa and its glands represent a close interactive barrier to the outside world. This delicate surface is protected by a multilayered mucus barrier which contains among others the mucins MUC5AC and MUC6 and the trefoil factor family peptide TFF2. Furthermore, two types of gastric glands form delicate homeostatic systems, i.e. the fundic and antral glands, which show continual bidirectional self-renewal via differentiation from stem and progenitor cells. It was the aim of this study to analyze the self-renewal of these gastric units. Material and methods. Three characteristic regions (i.e. foveolar, proliferative zone and lower gland regions) were isolated from fundic and antral units by the use of laser microdissection and expression profiles concerning known marker genes were generated by reverse transcription polymerase chain reaction (RT-PCR) analysis. Results. The surface mucous cells (SMCs) of fundic and antral units characteristically differed in the expression of certain secretory genes. Furthermore, the maturation of mucous neck cells and their trans-differentiation into chief cells as well as the maturation of antral SMCs and antral gland cells occurred in a stepwise manner. Discussion. The correct maturation particularly of mucous neck cells and their trans-differentiation into chief cells is critical for homeostatic self-renewal of fundic units. Dysregulation of this multistep process can result in generation of the spasmolytic polypeptide-expressing metaplasia (SPEM) lineage which is characterized by its strong ectopic TFF2 expression. Chronic inflammation is known to support SPEM formation. The SPEM lineage is a precancerous lesion which can further differentiate into intestinal metaplasia.