Extracellular Vesicles: Satellites of Information Transfer in Cancer and Stem Cell Biology

Abstract

The generation and shedding of extracellular vesicles (EVs), including exosomes and microvesicles (MVs), by cells has emerged as a form of intercellular communication with important roles in several physiological processes and diseases such as cancer. These membrane-enclosed packets can transfer specific proteins, RNA transcripts, microRNAs, and even DNA to target cells, thereby altering their function. Despite the exponential growth of the EV field, a great deal remains unclear about the mechanisms that regulate exosome and MV biogenesis, as well as about how to isolate different classes of EVs and how to best take advantage of them for clinical applications.

Figure 1. Diagram Highlighting How EVs Function as a Novel Form of Intercellular Communication

(Left) Most cell types generate two distinct types of EVs, exosomes and microvesicles (MVs). Exosomes (in red) are formed as a result of directing multi-vesicular bodies (MVBs) containing endosomes to the surface of a cell, where the MVBs fuse with the plasma membrane and release their contents (exosomes) into the extracellular space. In contrast, MVs (in blue) directly bud from the surface of a cell, are loaded with various cargo, and then are released or shed from the cell. (Right) Both exosomes and EVs are transferred to recipient cells, an outcome that often changes their phenotype. Some of the most common types of EV cargo are also listed.

Figure 2. Stem Cells Generate EVs that Can Affect Their Environment

Both adult stem cells and ESCs (blue cell on left) have been shown to release exosomes (red EVs) and MVs (blue EVs) into their surroundings. These EVs can be transferred to other stem cells (blue cell on right) to help maintain the stem cell niche by promoting cell growth (i.e., self-renewal). However, EVs from stem cells are also capable of being transferred to differentiated cell types (green cell on right) located within diseased or damaged tissue as a means to stimulate tissue regeneration (by promoting the growth and survival of the differentiated cell type). Moreover, EVs from stem cells have been shown to activate endothelial cells (red cell on right) found nearby diseased/damaged tissue to form new blood vessels (i.e., angiogenesis) as a mechanism to further stimulate regenerative processes.