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Feng, Tzu-Yu, Azar, Francesca N., Dreger, Sally A., Rosean, Claire Buchta, McGinty, Mitchell T., Putelo, Audrey M., Kolli, Sree H., Carey, Maureen A., Greenfield, Stephanie, Fowler, Wesley J., Robinson, Stephen D. 
ORCID: https://orcid.org/0000-0002-6606-7588 and Rutkowski, Melanie R.
(2022)
Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors.
Cancer Immunology Research, 10 (11).
1309–1325.
ISSN 2326-6074
Abstract
Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, before breast tumor initiation, enhances early dissemination of hormone receptor–positive (HR+) mammary tumor cells. Here, we sought to determine whether cellular changes occurring in normal mammary tissues, before tumor initiation and in response to dysbiosis, enhanced dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in normal, non–tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that profibrogenic mammary tissue mast cells from dysbiotic animals were sufficient to enhance dissemination of HR+ tumor cells. Using archival HR+ patient samples, we determined that enhanced collagen levels in tumor-adjacent mammary tissue positively correlated with mast cell abundance and HR+ breast cancer recurrence. Together, these data demonstrate that mast cells programmed by commensal dysbiosis activate mammary tissue fibroblasts and orchestrate early dissemination of HR+ breast tumors.
| Item Type: | Article |
|---|---|
| Additional Information: | The publication costs of this article were defrayed in part by the payment of publication fees. Therefore, and solely to indicate this fact, this article is hereby marked “advertisement” in accordance with 18 USC section 1734. Funding Information: the University of Virginia Comprehensive Cancer Center, CBR was supported by T32AI007496-21, MTM was supported by T32CA009109-46. S.D. Robinson and S.A. Dreger were supported by the BBSRC Institute Strategic Program Gut Microbes and Health BB/R012490/1 and its constituent project (BBS/E/F/000PR10355). S.D. Robinson and W.J. Fowler were also supported by Cancer Research UK (grant number C18281/A29019). The authors also wish to acknowledge the roles of the Breast Cancer Now Tissue Bank in collecting and making available the samples and/or data, and the patients who have generously donated their tissues and shared their data to be used in the generation of this publication. The authors are also grateful for the extraordinary support from the University of Virginia Comprehensive Cancer Center, the Center for Research Histology, Biorepository and Tissue Research Facility, Flow Cytometry Core Facility, Center for Comparative Medicine, Trans University Microbiome Initiative and the Carter Immunology Center. In addition, we would like to thank Dr. Jose R. Conejo-Garcia for the BRPKp110 HR+ breast tumor cell line, Dr. Paula D. Bos for the PyMT cell line, Dr. Kimberly D. Kelly for the NIH-3T3 fibroblast cell line, and Dr. Sanja Arandjelovic for critical reading of the article. |
| Uncontrolled Keywords: | medicine(all),sdg 3 - good health and well-being ,/dk/atira/pure/subjectarea/asjc/2700 |
| Faculty \ School: | Faculty of Science > School of Biological Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Cells and Tissues |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 21 Mar 2023 09:34 |
| Last Modified: | 08 Mar 2024 09:30 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/91621 |
| DOI: | 10.1158/2326-6066.CIR-21-1120 |
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