Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori -infected p27-deficient mice

// Songhua Zhang 1 , Woojin Kim 1 , Tu T. Pham 1 , Arlin B. Rogers 2 , Jean Marie Houghton 3 and Steven F. Moss 1 1 Division of Gastroenterology, Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI, USA 2 Department of Biomedical Sciences, Tufts Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA 3 Department of Medicine and Cancer Biology, Division of Gastroenterology, University of Massachusetts Medical School, Worcester, MA, USA Correspondence to: Steven F. Moss, email: // Keywords : Helicobacter pylori , gastric cancer, bone marrow transplantation, inflammation, cytokines Received : March 15, 2016 Accepted : September 02, 2016 Published : September 15, 2016 Abstract Objective: Chronic Helicobacter pylori ( H. pylori ) infection promotes non-cardia gastric cancer. Some mouse models suggest that bone marrow derived cells (BMDC) contribute to Helicobacter -associated gastric carcinogenesis. We determined whether this increased susceptibility to Helicobacter -induced gastric carcinogenesis of p27-deficient mice is dependent upon their p27-null BMDC or their p27-null gastric epithelial cells. Design: Female mice (recipients) were irradiated and transplanted with BMDC from male donors. Wild type (WT) mice in group 1 (control) received BMDC from male GFP-transgenic mice. Female WT and p27 KO mice were engrafted with male p27KO mice BMDC (Group 2) or GFP-transgenic WT BMDC (Group 3). Recipients were infected with H. pylori SS1 for one year. Results: Mice lacking p27 in either the BM pool or gastric epithelium developed significantly more advanced gastric pathology, including high-grade dysplasia. Co-staining of donor BMDC in dysplastic gastric glands was confirmed by immunofluorescence. Gastric expression of IL-1 beta protein was reduced in groups 2 and 3 ( p < 0.05 vs control) whereas expression of IFN-γ and chemokines MIP-1 beta, MIG, IP-10 and RANTES in group 2 were significantly higher than group 3. Conclusions: Both bone marrow-derived and gastric epithelial cells contribute to the increased gastric cancer susceptibility of p27-deficient H. pylori -infected mice.