Department of Medicine, Division of Gastroenterology
Cancer Biology | Digestive System Diseases | Gastroenterology | Neoplasms
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-gamma 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.
helicobacter pylori, bone marrow transplantation, cytokines, gastric cancer, inflammation
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DOI of Published Version
Oncotarget. 2016 Oct 25;7(43):69136-69148. doi: 10.18632/oncotarget.12049. Link to article on publisher's site
Zhang, Songhua; Kim, Woojin; Pham, Tu T.; Rogers, Arlin B.; Houghton, JeanMarie; and Moss, Steven F., "Native and bone marrow-derived cell mosaicism in gastric carcinoma in H. pylori-infected p27-deficient mice" (2016). Open Access Articles. 2970.
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This work is licensed under a Creative Commons Attribution 3.0 License.