Gut bacteria require neutrophils to promote mammary tumorigenesis
Author(s)Lakritz, Jessica; Poutahidis, Theofilos; Mirabal, Sheyla; Varian, Bernard; Levkovich, Tatiana; Ibrahim, Yassin; Ward, Jerrold M.; Teng, Ellen C.; Fisher, Brett; Parry, Nicola; Lesage, Stephanie; Alberg, Natalie; Gourishetti, Sravya; Fox, James G.; Ge, Zhongming; Erdman, Susan E.; ... Show more Show less
MetadataShow full item record
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.
DepartmentMassachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Division of Comparative Medicine
Impact Journals/National Center for Biotechnology Information (U.S.)
Lakritz, Jessica R., et al. "Gut bacteria require neutrophils to promote mammary tumorigenesis." Oncotarget, Vol. 6, No. 11 (2015). © 2015 Impact Journals, LLC.
Final published version