Gut bacteria require neutrophils to promote mammary tumorigenesis
| Autor: | James G. Fox, Bernard J. Varian, Sravya Gourishetti, Zhongming Ge, Jerrold M. Ward, Brett Fisher, Susan E. Erdman, Ellen C. Teng, Nicola Parry, Tatiana Levkovich, Jessica R. Lakritz, Theofilos Poutahidis, Yassin M. Ibrahim, Sheyla Mirabal, Natalie Alberg, Stephanie Lesage |
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| Rok vydání: | 2015 |
| Předmět: |
Carcinogenesis
Neutrophils Mammary Neoplasms Animal Mice Transgenic medicine.disease_cause Helicobacter Infections Mice Immune system Breast cancer mammary cancer medicine Animals Gastrointestinal tract Mammary tumor Bacteria biology Microbiota enteric Cancer medicine.disease biology.organism_classification 3. Good health Intestines immune system Oncology Immunology biology.protein Female Helicobacter hepaticus Antibody microbes Research Paper |
| Zdroj: | Oncotarget |
| ISSN: | 1949-2553 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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