UMMS Affiliation

Department of Medicine, Division of Gastroenterology

Date

10-25-2016

Document Type

Article

Disciplines

Cancer Biology | Digestive System Diseases | Gastroenterology | Neoplasms

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-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.

Rights and Permissions

Citation: Oncotarget. 2016 Oct 25;7(43):69136-69148. doi: 10.18632/oncotarget.12049. Link to article on publisher's site. All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.

DOI of Published Version

10.18632/oncotarget.12049

Related Resources

Link to Article in PubMed

Keywords

helicobacter pylori, bone marrow transplantation, cytokines, gastric cancer, inflammation

Journal Title

Oncotarget

PubMed ID

27655701

Creative Commons License

Creative Commons Attribution 3.0 License
This work is licensed under a Creative Commons Attribution 3.0 License.

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