Emerging picture of the distinct traits and functions of microvesicles and exosomes

The ability of a cell to receive signals from other cells and then translate them into changes in cell behavior plays crucial roles in development and tissue homeostasis. However, the deregulation of these carefully orchestrated events underlie the onset or progression of several diseases in the adult organism, highlighting the need to better understand the mechanisms through which cells communicate with each other. When considering various examples of cell–cell communication, the well-established growth factor receptor signaling paradigm comes to mind. In this case, one cell secretes a soluble growth factor into the extracellular environment. The growth factor then binds to its corresponding receptor expressed on the surface of a second cell, resulting in its activation and the initiation of intracellular signaling events that control a myriad of cellular processes ranging from promoting cell growth and differentiation to cell death and migration. In PNAS, Kanada et al. investigate what is emerging as a new and exciting mechanism used by cancer cells to communicate with their environment. It entails the ability of cells to generate and release two types of cargo-containing vesicular structures, collectively referred to as extracellular vesicles (EVs) that are generally believed to differ in their biogenesis and certain physical properties. One of these types of EVs is exosomes, which are generated as a result of trafficking multivesicular bodies containing endosomes from the cytosol to the cell surface. The multivesicular bodies then fuse with the plasma membrane, releasing the endosomes (now widely referred to as exosomes) into the extracellular space. Most studies that have analyzed exosomes indicate that they range in size from 30 to 80 nm in diameter. Microvesicles (MVs), which represent the other major class of EVs, are considerably larger than exosomes (200–1,500 nm in size) and are generated as an outcome of plasma membrane budding. Both exosomes and MVs are able to engage and transfer their cargo to other (recipient) cells, whereupon they significantly influence cellular processes. In their study, Kanada et al. isolated the different populations of EVs produced by HEK293FT cells and meticulously compared their physical properties, ability to be loaded with different types of cargo, and function. Their findings not only challenged some of the central dogmas in the field but also raised the interesting possibility that EVs might provide an effective delivery mechanism for gene therapy. (read more…)