Reciprocal interactions between the gut microbiome and mammary tissue mast cells promote metastatic dissemination of HR+ breast tumors

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

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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
Uncontrolled Keywords:	sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	LivePure Connector
Date Deposited:	21 Mar 2023 09:34
Last Modified:	21 Apr 2023 01:36
URI:	https://ueaeprints.uea.ac.uk/id/eprint/91621
DOI:	10.1158/2326-6066.CIR-21-1120

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