Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR+ Breast Tumors
Institution: Department of Microbiology Immunology and Cancer Biology, University of Virginia
Corresponding Researcher: Melanie Rutkowski
Data Link(s): NA
Keyword(s): IHC, tumor-adjacent, dysbiosis, hormone-receptor positive
Summary
Establishing commensal dysbiosis, defined as an inflammatory gut microbiome with low biodiversity, prior to 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, prior to tumor initiation and in response to dysbiosis, enhance dissemination of HR+ tumors. Commensal dysbiosis increased both the frequency and profibrogenicity of mast cells in the normal non-tumor-bearing mammary tissues, a phenotypic change that persisted after tumor implantation. Pharmacological and adoptive transfer approaches demonstrated that pro-fibrogenic 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.
