Exosome mediated phenotypic changes in lung cancer pathophysiology

Yoshihisa Shimada, John D. Minna


Exosomes are small extracellular vesicles with a size range of 40–150 nm and a lipid bilayer membrane (1-4). They contain protein and nucleic acids, and mediate local and systemic intercellular communication (1-3). Many cell types can produce exosomes, the contents of which likely reflect the phenotypic states of the cells that generate them under both physiological and pathological conditions. They may convey these exosomal cargoes to neighboring or distant cells, and subsequently modulate the phenotype of these target cells. At first exosomes were thought to function as “cellular garbage bags”, but now these nanosized extracellular vesicles are being studied for their role in progression and metastasis (5). Cancer-derived exosomes are reported to play a role in various malignant phenotype mechanisms such as proliferation, motility, invasive properties of the recipient cells, epithelial-mesenchymal transition (EMT), transferring drug resistance, immune evasion, and pre-metastatic niche formation (6-17). However, we still need to understand how exosomes and their cargoes function in recipient cells, and whether exosome packaging and release in the extracellular space is an active or passive process.