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Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer.
- Source :
-
Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2022 Feb 22; Vol. 28, pp. 17-31. Date of Electronic Publication: 2022 Feb 22 (Print Publication: 2022). - Publication Year :
- 2022
-
Abstract
- Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. TNBC progression is sustained by recruitment of a strong tumor microenvironment (TME) mainly composed of cancer-associated fibroblasts (CAFs) able to endorse tumor hallmarks. Increasing evidences demonstrate that exosomes mediate the crosstalk between cancer cells and the TME. We examined TNBC-derived exosomes and their microRNA (miRNA) cargo in activation of normal fibroblasts (NFs) toward CAFs. We demonstrated that TNBC cell-derived exosomes increased NF collagen contraction and migration alongside CAF molecular markers. Exosome-activated fibroblasts promoted the invasion potential of normal breast epithelial cells, as assessed by an organotypic co-culture assay that resembled the in vivo context. We also investigated TNBC cell-derived exosome cargo in activating NFs to CAFs by performing small RNA sequencing. We found that the synergistic action of miR-185-5p, miR-652-5p, and miR-1246 boosted fibroblast migration and contraction, promoting specific CAF subspecialization toward a pro-migratory functional state. These data highlight the role of breast cancer cells in re-education of the TME and their contribution to tumor evolution.<br />Competing Interests: The authors declare no competing interests.<br /> (© 2022 The Author(s).)
Details
- Language :
- English
- ISSN :
- 2162-2531
- Volume :
- 28
- Database :
- MEDLINE
- Journal :
- Molecular therapy. Nucleic acids
- Publication Type :
- Academic Journal
- Accession number :
- 35317202
- Full Text :
- https://doi.org/10.1016/j.omtn.2022.02.013