Reciprocal Interactions Between the Gut Microbiome and Mammary Tissue Mast Cells Promote Metastatic Dissemination of HR+ Breast Tumors.

Autor:	Feng TY; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Azar FN; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Dreger SA; Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom., Rosean CB; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., McGinty MT; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Putelo AM; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Kolli SH; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Carey MA; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia.; Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia., Greenfield S; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia., Fowler WJ; Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom., Robinson SD; Gut Microbes and Health Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, United Kingdom.; School of Biological Sciences, University of East Anglia, Norwich Research Park, Norwich, United Kingdom., Rutkowski MR; Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, Virginia.
Jazyk:	angličtina
Zdroj:	Cancer immunology research [Cancer Immunol Res] 2022 Nov 02; Vol. 10 (11), pp. 1309-1325.
DOI:	10.1158/2326-6066.CIR-21-1120
Abstrakt:	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. (©2022 American Association for Cancer Research.)
Databáze:	MEDLINE
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