Helicobacter pylori, gastric cancer and gastric cancer stem cells

Chronic Helicobacter pylori (H. pylori) infection is considered the main cause of gastric cancer (GC). Gastric carcinogenesis is the result of a series of precancerous changes from atrophic gastritis to intestinal metaplasia and dysplasia in which H. pylori plays a key role both through direct and indirect mechanisms. Chronic inflammation caused by H. pylori infection leads to gastric mucosal damage and consequently increases turnover in gastric epithelium. During this process, resident stem cells may, over time, accumulate genetic and epigenetic changes inducing an aberrant phenotype and thus leading to the emergence of GC stem cells. Furthermore, H. pylori has direct oncogenic properties regarded to the cytotoxin-associated gene A (CagA). This bacterial oncoprotein is delivered into host cells and promotes neoplastic transformation by interacting with several intracellular signaling pathways. In addition, chronic inflammation and tissue injury followed by recruitment and engraftment of bone marrow derived stem cells into the gastric epithelium, may represent another source of GC stem cells. In this scenario, GC stem cells have been identified as the cell compartment able of self-renewal and differentiation responsible of tumor continuous growth. The possibility to isolate and identify these cells via specific surface markers may provide, in the future, novel targets to develop specific molecules able to prevent GC development or to counteract tumor evolution.