Gut bacteria require neutrophils to promote mammary tumorigenesis
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 m...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Impact Journals/National Center for Biotechnology Information (U.S.)
2015
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| Online Access: | http://hdl.handle.net/1721.1/97139 https://orcid.org/0000-0001-9307-6116 |
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| author | 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. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering 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. |
| author_sort | Lakritz, Jessica |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:42:08Z |
| format | Article |
| id | mit-1721.1/97139 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:42:08Z |
| publishDate | 2015 |
| publisher | Impact Journals/National Center for Biotechnology Information (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/971392022-09-29T15:32:59Z Gut bacteria require neutrophils to promote mammary tumorigenesis 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. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Division of Comparative Medicine Lakritz, Jessica Poutahidis, Theofilos Mirabal, Sheyla Varian, Bernard Levkovich, Tatiana Ibrahim, Yassin Teng, Ellen C. Fisher, Brett Parry, Nicola Lesage, Stephanie Alberg, Natalie Gourishetti, Sravya Fox, James G. Ge, Zhongming Erdman, Susan E. 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. National Institutes of Health (U.S.) (Grant U01 CA164337) National Institutes of Health (U.S.) (Grant T32 OD011141) 2015-06-01T16:52:54Z 2015-06-01T16:52:54Z 2015-03 2015-01 Article http://purl.org/eprint/type/JournalArticle 1949-2553 http://hdl.handle.net/1721.1/97139 Lakritz, Jessica R., et al. "Gut bacteria require neutrophils to promote mammary tumorigenesis." Oncotarget, Vol. 6, No. 11 (2015). © 2015 Impact Journals, LLC. https://orcid.org/0000-0001-9307-6116 en_US http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path[]=3328 Oncotarget Creative Commons Attribution http://creativecommons.org/licenses/by/3.0/ application/pdf Impact Journals/National Center for Biotechnology Information (U.S.) Impact Journals/National Center for Biotechnology Information (U.S.) |
| spellingShingle | 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. Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title | Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title_full | Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title_fullStr | Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title_full_unstemmed | Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title_short | Gut bacteria require neutrophils to promote mammary tumorigenesis |
| title_sort | gut bacteria require neutrophils to promote mammary tumorigenesis |
| url | http://hdl.handle.net/1721.1/97139 https://orcid.org/0000-0001-9307-6116 |
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