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Communication by Extracellular Vesicles Where We Are and Where We Need to Go.pdf

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Communication by Extracellular Vesicles Where We Are and Where We Need to Go

Leading Edge ReviewCommunication by Extracellular Vesicles: Where We Are and Where We Need to GoMercedes Tkach1 and Clotilde The?ry1,* 1Institut Curie, PSL Research University, INSERM U932, 75005 Paris, France *Correspondence: clotilde.thery@curie.fr /10.1016/j.cell.2016.01.043 In multicellular organisms, distant cells can exchange information by sending out signals com- posed of singlemolecules or, as increasingly exemplified in the literature, via complex packets stuf- fed with a selection of proteins, lipids, and nucleic acids, called extracellular vesicles (EVs; also known as exosomes and microvesicles, among other names). This Review covers some of the most striking functions described for EV secretion but also presents the limitations on our knowl- edge of their physiological roles. While there are initial indications that EV-mediated pathways op- erate in vivo, the actual nature of the EVs involved in these effects still needs to be clarified. Here, we focus on the context of tumor cells and their microenvironment, but similar results and challenges apply to all patho/physiological systems in which EV-mediated communication is proposed to take place.Introduction Cells can communicate with neighboring cells or with distant cells through the secretion of extracellular vesicles (EVs). EVs are composed of a lipid bilayer containing transmembrane pro- teins and enclosing cytosolic proteins and RNA. Cells can secrete different types of EVs that have been classified accord- ing to their sub-cellular origin (Colombo et al., 2014). On one hand, EVs can be formed and released by budding from the cells’ plasma membrane. These EVs display a diverse range of sizes (100–1,000 nm in diameter) and are generally known in the literature as microvesicles, ectosomes, or microparticles. Other types of vesicles, the exosomes, are generated inside multive- sicular endosomes or multivesicular bodies (MVBs) and are secreted when these compartments fuse with the plasma mem- brane. Exo