Gut bacteria require neutrophils to promote mammary tumorigenesis
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Lakritz_3328-46347-3-PB.pdf
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Author(s)
Lakritz, Jessica
Poutahidis, Theofilos
Mirabal, Sheyla
Varian, Bernard
Levkovich, Tatiana
Ibrahim, Yassin
Ward, Jerrold M.
Teng, Ellen C.
Fisher, Brett
Parry, Nicola
Date Issued
March 2015
Journal
Oncotarget
Publisher
Impact Journals/National Center for Biotechnology Information (U.S.)
Citation
Lakritz, Jessica R., et al. "Gut bacteria require neutrophils to promote mammary tumorigenesis." Oncotarget, Vol. 6, No. 11 (2015). © 2015 Impact Journals, LLC.
Version
Final published version
Abstract
Recent studies suggest that gastrointestinal tract microbiota modulate cancer development in distant non-intestinal tissues. Here we tested mechanistic hypotheses using a targeted pathogenic gut microbial infection animal model with a predilection to breast cancer. FVB-Tg(C3-1-TAg)cJeg/JegJ female mice were infected by gastric gavage with Helicobacter hepaticus at three-months-of-age putting them at increased risk for mammary tumor development. Tumorigenesis was multifocal and characterized by extensive infiltrates of myeloperoxidase-positive neutrophils otherwise implicated in cancer progression in humans and animal models. To test whether neutrophils were important in etiopathogenesis in this bacteria-triggered model system, we next systemically depleted mice of neutrophils using thrice weekly intraperitoneal injections with anti-Ly-6G antibody. We found that antibody depletion entirely inhibited tumor development in this H. hepaticus-infected model. These data demonstrate that host neutrophil-associated immune responses to intestinal tract microbes significantly impact cancer progression in distal tissues such as mammary glands, and identify gut microbes as novel targets for extra-intestinal cancer therapy.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Division of Comparative Medicine
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Creative Commons Attribution
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DOI of Published Version
http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3328
