Fig. 1

Biogenesis, secretion, and uptake of exosomes. Endocytosis often occurs at lipid rafts containing a variety of tumor-specific receptors and common membrane proteins, such as tetraspanins (eg, CD9, CD63, CD81), MHC I and II, and adhesion molecules (eg, integrins, cadherins), and results in the formation of early endosomes. Exosomes show inward budding of the multivesicular bodies (MVB). During this process, numerous proteins (e.g. receptor, ubiquitin-related proteins, heat shock proteins), nucleic acid (e.g. miRNAs, RNAs, DNAs, lnRNAs), transcriptional factors, and lipids (e.g., cholesterol, ceramide) can be selectively packed into MVB in a cell type-dependent manner. After early-to-late endosome conversion, late endosomes containing MVB fuse with the plasma membrane to secrete exosomes toward the extracellular space by exocytosis, which is mainly controlled by endosome-specific Rab GTPases, including Rab11/35, Rab7, and Rab27. The uptake of exosomes by recipient cells can be mediated by a) direct fusion of exosomes with the cell membrane of the recipients, b) by receptor-ligand interactions, or c) by endocytosis