CXCR4-expressing progenitors in the gastric antrum contribute to gastric cancer development.

was recently shown to identify a discrete population of stem cells within the isthmus of the oxyntic gland within the gastric corpus. Chief cells at the base of the gastric corpus also express . The relevance of expression as a marker of specific cell populations within the antral glands of the distal stomach, however, is unknown. Using -CreERT mice, we revealed that antral cells, distinct from the population in the corpus, comprise long-lived progenitors that reside within the antral isthmus above or CCK2R cells. antral progenitors can serve as an origin of antral tumors induced by loss of Apc or MNU treatment. antral progenitors, as well as other antral stem/progenitor population, express Cxcr4, and are located in close proximity to Cxcl12 (the Cxcr4 ligand)-expressing endothelium. During antral carcinogenesis, there is an expansion of Cxcr4 epithelial cells as well as the Cxcl12 perivascular niche. Deletion of Cxcl12 in endothelial cells or pharmacological blockade of Cxcr4 inhibits antral tumor growth. Cxcl12/Cxcr4 signaling may be a potential therapeutic target.