Laboratory of Molecular Angiogenesis, GIGA Research Centre, University of Liège, Liège, Belgium.
Laboratory of Gene Expression and Cancer, GIGA-MBD, University of Liège, Liège, Belgium.
J Extracell Vesicles. 2022 Jun;11(6):e12228. doi: 10.1002/jev2.12228.
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.
肿瘤衍生的细胞外囊泡 (EVs) 通过调节血管生成和炎症等各种生理过程参与肿瘤进展。在这里，我们报告说，乳腺肿瘤环境中内皮细胞释放的 EVs 参与了肿瘤内巨噬细胞的募集，导致允许肿瘤生长的免疫调节表型。使用 RNA-Seq 方法，我们鉴定了几种在内皮细胞 EV 中发现的 microRNAs (miRNAs)，它们具有共同的靶标，参与免疫系统的调节。为了在小鼠肿瘤模型中进一步研究这些 miRNAs 的影响，我们专注于三种在人类和小鼠之间保守的 miRNAs，即 miR-142-5p、miR-183-5p 和 miR-222-3p。这些 miRNAs 在内皮细胞的肿瘤微环境中释放，并通过 EV 转移到巨噬细胞中。在小鼠乳腺肿瘤模型中，用富含这些 miRNAs 的 EV 处理会导致巨噬细胞向 M2 样表型极化，进而促进肿瘤生长。
