Exosomal microRNAs synergistically trigger stromal fibroblasts in breast cancer

• Main Authors: Iolanda Scognamiglio (Author), Lorenza Cocca (Author), Ilaria Puoti (Author), Francesco Palma (Author), Francesco Ingenito (Author), Cristina Quintavalle (Author), Alessandra Affinito (Author), Giuseppina Roscigno (Author), Silvia Nuzzo (Author), Rosario Vincenzo Chianese (Author), Stefania Belli (Author), Guglielmo Thomas (Author), Timo Schomann (Author), Alan Chan (Author), Maria Patrizia Stoppelli (Author), Gerolama Condorelli (Author)
• Format: Book
• Published: Elsevier, 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

2162-2531
10.1016/j.omtn.2022.02.013