Abstract
Extracellular vesicles (EVs) are produced by healthy tissues and tumor cells and are released in various bodily fluids, including blood. They are limited by bilayer phospholipidic membranes, and they carry a rich content in biomolecules. Their release cleanses the cells of their waste or serves as functional local and distant cell–cell communication and molecular exchange particles. This rich and heterogeneous content has been given intense attention in cancer physiopathology because EVs support cancer control and progression. Because of their specific active cargo, they are being evaluated as carriers of liquid biopsy biomarkers. Compared to soluble circulating biomarkers, their complexity might provide rich information on tumor and metastases status. Thanks to the acquired genomic changes commonly observed in oncogenic processes, double-stranded DNA (dsDNA) in EVs might be the latest most promising biomarker of tumor presence and complexity. This review will focus on the recent knowledge on the DNA inclusion in vesicles, the technical aspects of EV-DNA detection and quantification, and the use of EV-DNA as a clinical biomarker.
Highlights
Extracellular vesicles (EVs) have long been observed, but they were mostly considered as garbage bags to get rid of unusable intracellular constituents (Johnstone, 1992)
As liquid biopsies have been given more and more consideration for cancer patient management, a lot of attention and technical development aimed at detecting circulating cell free DNA, especially circulating tumor DNA within total cfDNA
Exosomal and EV-associated DNA seem promising as circulating biomarkers for cancer profiling as they can reflect the primary tumor and its metastases
Summary
Extracellular vesicles (EVs) have long been observed, but they were mostly considered as garbage bags to get rid of unusable intracellular constituents (Johnstone, 1992). EVs could bring complex signals through their membrane and by releasing the content of their lumen in the recipient cell, enabling horizontal transfer of proteins and RNAs (Cocucci et al, 2009) These concepts shed a new light on cell–cell communication, thought to occur until only by soluble signals decoded upon receptor binding or by connexons. A swift increase in EV literature occurred, and a lot of attention was given to the identification of the protein and RNA (including miRs) cargoed in EVs as biomarkers in cancer. Another important type of EV biomolecules emerges as relevant for cancer biology: the EV-DNA. The aim of this review is not to propose a complete description of EV generation, release, and outcome but to focus on their DNA content as a valuable material for cell–cell communication and a relevant biomarker in cancer clinical biology
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