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Panminerva Medica 2014 December;56(4):289-300

Copyright © 2014 EDIZIONI MINERVA MEDICA

language: English

Gastric cancer as a stem-cell disease: data and hypotheses

Fagoonee S. ¹, Li H. ², Zhang H. ², Altruda F. ³, Pellicano R. ⁴ ✉

¹ Institute for Biostructures and Bioimages-CNR c/o Molecular Biotechnology Center, University of Turin, Turin, Italy; ² Division of Gastroenterology, University of Massachusetts Medical School, Worcester MA, USA; ³ Molecular Biotechnology Center, University of Turin, Turin, Italy; ⁴ Department of Gastroenterology and Hepatology, Molinette Hospital, Turin, Italy

The main function of gastric stem cells is to maintain the integrity of the gastrointestinal epithelium and replenish all the mature cell lineages. In order to accomplish this, gastric stem cells proliferate and self-renew, giving rise to transient amplifying cells which replace the constantly renewing epithelium, especially after injury induced by long-term inflammation. Gastric cancer (GC) remains the fourth most common cancer and the second leading cause of death for cancer in the world. The most accepted model of gastric carcinogenesis provides a multifactorial and multistep pathogenesis, involving a number of initiators and other continuator agents. Helicobacter pylori infection is recognized as a necessary but insufficient cause of GC. Recent advances in gastric stem cell biology point out to two hypotheses. In the first, it is postulated that resident stem cells may, in a chronically inflamed environment, as in the case of Helicobacter pylori-induced gastritis, accumulate over time a series of genetic and epigenetic changes that lead to the emergence of GC stem cells. Alternatively, the setting of chronic inflammatory stress may lead to loss of the indigenous gastric stem cells from their niches, followed by recruitment and engraftment of bone marrow derived stem cells (BMDCs) into the gastric epithelium. In the mouse model, increasing evidence supports the hypothesis that BMDCs are important cellular source of Helicobacter-induced GC. This review highlights data and hypotheses about GC as a model of stem-cell disease.