Tumor microenvironment affects the composition of endothelial-derived exosomes: impact in tumor 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 exosomes 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 exosomes released by target cells is poorly studied. Consequently, we sought to determine the composition of exosomes released by ECs under tumor microenvironment, and to assess whether these vesicles present different functional properties. Using RNA-seq approaches, we demonstrated that exosomes released by ECs in tumor microenvironment context present a specific repertory of microRNAs associated to tumor angiogenesis and inflammatory pathways. Furthermore, we showed that these vesicles were able to optimize inflammatory response of immune cells by transferring several dysregulated microRNAs. Currently, we are identifying the molecular pathways modulated by endothelial-derived exosomes in tumor microenvironment.