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Abstract :
[en] Breast cancer (BC) is one of the most common cancers worldwide. While it can be treated, metastatic BC remains incurable. Previously, our research group demonstrated that endothelial cell-derived extracellular vesicles (EVs) enriched in miR-142-5p, miR-183-5p, and miR-222-3p participate in the polarization of macrophages towards an M2-like phenotype, thus promoting tumour growth in a BC mouse model (Njock et al., 2022, JEV). However, the impact of these microRNAs on metastasis remains unknown. A crucial step during metastasis is the formation of a pre-metastatic niche (PMN), which is notably initiated by EVs.
With this project, we aim to unravel the impact of these microRNAs on PMN formation and metastasis in vitro and in vivo (Fig. 1).
Figure 1 - Graphical abstract.
In this study, we isolated EVs from mouse endothelial cell lines, characterized them using Western blotting (WB) and Nanosight Tracking Analysis (NTA). Next, we evaluated their incorporation into macrophages and fibroblasts, which are two major cell types in PMN formation, using confocal microscopy. Afterwards, we electroporated the EVs with the three microRNAs and added them to macrophages and fibroblasts. To determine the effects of these EVs on cell differentiation, we analysed the expression by qPCR of several genes known to be involved in PMN formation.
Our data showed that endothelial EVs were successfully incorporated into the recipient cells. Our qPCR results demonstrated that microRNA-enriched EVs upregulate the expression of pro-tumorigenic genes Csf3, Cxcl1, Col3a1, Il-1β, and Ccl3. Currently, we are further investigating the role of microRNA-enriched endothelial EVs in PMN formation in a 4T1-BC mouse model.
Our current findings reveal a previously unrecognized role of microRNA-enriched endothelial EVs on macrophage and fibroblast differentiation in vitro. These preliminary findings reveal a potential role of endothelial EVs in PMN formation, offering avenues for novel approaches in BC treatment.
