Helicobacter pyloriinduces the expression of Lgr5 and stem cell properties in gastric target cells

Abstract

Helicobacter pyloriinfection predisposes carriers to a high risk of developing gastric cancer. The cell-of-origin of antral gastric cancer is the Lgr5+stem cell. Here, we show that infection of antrum-derived gastric organoid cells withH. pyloriincreases the expression of the stem cell marker Lgr5 as determined by immunofluorescence microscopy, qRT-PCR, and Western blotting, both when cells are grown and infected as monolayers and when cells are exposed toH. pyloriin 3D structures.H. pyloriexposure increases stemness properties as determined by spheroid formation assay. Lgr5 expression and the acquisition of stemness depend on a functional type IV secretion system (T4SS) and at least partly on the T4SS effector CagA. The pharmacological inhibition or genetic ablation of NF-κB reverses the increase in Lgr5 and spheroid formation. Constitutively active Wnt/β-catenin signaling because ofApcinactivation exacerbatesH. pylori–induced Lgr5 expression and stemness, both of which persist even after eradication of the infection. The combined data indicate thatH. pylorihas stemness-inducing properties that depend on its ability to activate NF-κB signaling.