TAM; breast cancer; extracellular vesicles; macrophages; microRNA; MicroRNAs; Animals; Disease Models, Animal; Endothelial Cells; Mice; Tumor Microenvironment; Tumor-Associated Macrophages; Extracellular Vesicles/genetics; MicroRNAs/genetics; Neoplasms; Cell Biology; Histology
[en] Tumour-derived extracellular vesicles (EVs) participate in tumour progression by deregulating various physiological processes including angiogenesis and inflammation. Here we report that EVs released by endothelial cells in a mammary tumour environment participate in the recruitment of macrophages within the tumour, leading to an immunomodulatory phenotype permissive for tumour growth. Using RNA-Seq approaches, we identified several microRNAs (miRNAs) found in endothelial EVs sharing common targets involved in the regulation of the immune system. To further study the impact of these miRNAs in a mouse tumour model, we focused on three miRNAs that are conserved between humans and mouse, that is, miR-142-5p, miR-183-5p and miR-222-3p. These miRNAs are released from endothelial cells in a tumour microenvironment and are transferred via EVs to macrophages. In mouse mammary tumour models, treatment with EVs enriched in these miRNAs leads to a polarization of macrophages toward an M2-like phenotype, which in turn promotes tumour growth.
Funding text :
This study was supported by the University of Liège (ARC: RNAngio), the FNRS (Fonds National de la Recherche Scientifique, Belgium) (PDR T 1096.14), and the Léon Frédéricq fund. Computational resources have been provided by the Consortium des Équipements de Calcul Intensif (CÉCI), funded by the Fonds de la Recherche Scientifique de Belgique (F.R.S.-FNRS) under Grant No. 2.5020.11 and by the Walloon Region.