From Exosome Biogenesis to Absorption: Key Takeaways for Cancer Research

SIMPLE SUMMARY: Exosomes are nanometer-sized vesicles released by different cells that are important in the normal functioning of the body. In cancer, exosomes have been found to promote tumor growth and metastasis by carrying functional biomolecules and acting on different target sites in the body. Understanding the mechanism by which cancers modulate exosome secretion is crucial to studying cancer biology and developing new therapeutic approaches. Herein, we summarize the biological processes involved in the generation of exosomes, and the factors affecting the targeting and internalization of exosomes. By outlining the mechanisms regulating exosome dynamics, we link exosome secretion with characteristics of cancer cells and suggest methods for improving future research. ABSTRACT: Exosomes are mediators of intercellular communication in normal physiology and diseases. While many studies have emerged on the function of exosomal cargoes, questions remain regarding the origin of these exosomes. The packaging and secretion of exosomes in different contexts modify exosomal composition, which may in turn impact delivery, uptake and cargo function in recipient cells. A mechanistic understanding of exosome biology is therefore crucial to investigating exosomal function in complex biological systems and to the development of novel therapeutic approaches. Here, we outline the steps in exosome biogenesis, including endosome formation, MVB formation, cargo sorting and extracellular release, as well as exosome absorption, including targeting, interaction with recipient cells and the fate of internalized exosomes. In addition to providing a framework of exosome dynamics, we summarize current evidence on major pathways and regulatory mechanisms. We also highlight the various mechanisms observed in cancer and point out directions to improve study design in exosome biology. Further research is needed to illuminate the relationship between exosome biogenesis and function, which will aid the development of translational applications.