Extracellular vesicles (EVs) are heterogeneous multi-signal messengers that support cancer growth and dissemination by mediating the tumor-stroma crosstalk. Exosomes are a subtype of EVs that originate from the limiting membrane of late endosomes, and as such contain information linked to both the intrinsic cell “state” and the extracellular signals cells received from their environment. Resolving the signals affecting exosome biogenesis, cargo sorting and release will increase our understanding of tumorigenesis. Researchers from the VU University Medical Center, Amsterdam highlight key cell biological processes that couple exosome biogenesis to cargo sorting in cancer cells. Moreover, they discuss how the bidirectional communication between tumor and non-malignant cells affect cancer growth and metastatic behavior.
Schematic representation of EV biogenesis pathway
While microvesicles bud directly from the plasma membrane, exosomes are generated within MVB subpopulations that upon maturation fuse with the plasma membrane. Alternative MVB pathways include fusion with lysosomes or with autophagosomes, although little is known about the mechanisms determining MVB fate. MVB fusion with the plasma membrane is a tightly regulated multistep process that includes MVB trafficking along microtubules, docking at the plasma membrane and SNARE-mediated fusion.