Tumour microenvironment affects the composition of endothelial cell-derived extracellular vesicles: impact in tumour progression

The tumor microenvironment plays a crucial role in the progression of tumor growth and metastasis by deregulating various physiological processes including angiogenesis and inflammation. Several studies have previously demonstrated that tumor-derived extracellular vesicles (EVs) are actively involved in the mediation of tumorigenesis by “reprogramming” target cells (e.g. endothelial cells (ECs)) through transfer of pro-angiogenic microRNAs. But the function of EVs released by target cells is poorly studied. Consequently, we sought to determine the composition of EVs released by ECs under tumor microenvironment, and to assess whether these vesicles present different functional properties. Using RNA-seq approaches, we demonstrated that EVs released by ECs in tumor microenvironment context present a specific repertory of microRNAs associated to tumor angiogenesis and inflammatory pathways. Interestingly, some of the dysregulated microRNAs are differently expressed at the cellular and exosomal levels. Furthermore, we showed that these vesicles were able to deregulate angiogenesis pathway by transferring several dysregulated microRNAs to target cells. Currently, we are identifying the molecular targets and pathways modulated by EC-derived EVs under tumor microenvironment.