Fig. 2.

Biogenesis of EVs and mechanisms of signal transduction. Exosomes are released from cells into the extracellular space by fusion of endosomes (multivesicular bodies) with the plasma membrane of the cell (1). In contrast, microvesicles are formed directly at the plasma membrane and bud from its lipid bilayer (2). In apoptotic cells, membrane protrusions are formed and release vesicles from their top (3), and apoptotic bodies of heterogenic size and morphology are generated as the cell dissolves (4). In tumor cells large EVs termed oncosomes can bleb of the plasma membrane into the extracellular space (5). There are several ways how EVs can transmit information to target cells: (i) they can undergo lysis in the extracellular space (6), releasing their cargo and membrane components, which can then bind to receptors on cell surfaces (7); (ii) surface molecules of intact EVs can stimulate receptors on target cells (8); and (iii) EVs can be incorporated by cells, and release their content through membrane fusion (9), or undergo endocytosis (10) being transferred into endosomes (11) with either lysosomal degradation (12), or escape from the endosome delivering the EV’s cargo into the target cell’s cytoplasm (13). Modified from “Extracellular Vesicles: Unique Intercellular Delivery Vehicles” [21]