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.
CITATION STYLE
Feng, T. Y., Azar, F. N., Dreger, S. A., Rosean, C. B., McGinty, M. T., Putelo, A. M., … Rutkowski, M. 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. https://doi.org/10.1158/2326-6066.CIR-21-1120
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