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// Jessica R. Lakritz 1 , Theofilos Poutahidis 1, 2 , Sheyla Mirabal 1 , Bernard J. Varian 1 , Tatiana Levkovich 1 , Yassin M. Ibrahim 1 , Jerrold M. Ward 3 , Ellen C. Teng 1 , Brett Fisher 1 , Nicola Parry 1 , Stephanie Lesage 1 , Natalie Alberg 1 , Sravya Gourishetti 1 , James G. Fox 1 , Zhongming Ge 1 , Susan E. Erdman 1 1 Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA 2 Laboratory of Pathology, Faculty of Veterinary Medicine, Aristotle University of Thessaloniki, Greece 54124 3 Global VetPathology, Montgomery Village, MD 20886, USA Correspondence to: Susan E. Erdman, e-mail: serdman@mit.edu Keywords: enteric, bacteria, microbes, mammary cancer, immune system Received: January 05, 2015 Accepted: February 09, 2015 Published: March 20, 2015 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.
Lakritz et al. (Fri,) studied this question.