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Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice
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Songhua Zhang1, Woojin Kim1, Tu T. Pham1, Arlin B. Rogers2, Jean Marie Houghton3 and Steven F. Moss1
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
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
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.
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