Extracellular vesicles and cancer therapy

Oxidative stress plays a significant role in cancer development and cancer therapy, and is a major contributor to normal tissue injury. The unique characteristics of extracellular vesicles (EVs) have made them potentially useful as a diagnostic tool in that their molecular content indicates their cell of origin and their lipid membrane protects the content from enzymatic degradation. In addition to their possible use as a diagnostic tool, their role in how normal and diseased cells communicate is of high research interest. The most exciting area is the association of EVs, oxidative stress, and pathogenesis of numerous diseases. However, the relationship between oxidative stress and oxidative modifications of EVs is still unclear, which limits full understanding of the clinical potential of EVs. Researchers from the University of Kentucky discuss how EVs, oxidative stress, and cancer therapy relate to one another; how oxidative stress can contribute to the generation of EVs; and how EVs’ contents reveal the presence of oxidative stress. They also point out the potential promise and limitations of using oxidatively modified EVs as biomarkers of cancer and tissue injury with a focus on pediatric oncology patients.

Biogenesis of exosomes and microvesicles

(A) Exosomes are derived from fusion of multivesicular endosomal bodies with the plasma membrane, which releases exosomes into extracellular space. Early endosomes are formed by the inward budding of either the plasma membrane or the Golgi Apparatus, where they then mature to late endosomes and become MVBs. The MVBs are then trafficked to the cell membrane, where they are fused with the plasma membrane by SNARE proteins. (B) Microvesicles are formed by the rearrangement of the plasma membrane facilitated by flippase, floppase, scrambalase, and calpain, leading to the budding of the microvesicles from the cell membrane.