DNA in extracellular vesicles: biological and clinical aspects

Elzanowska, Julia; Semira, Christine; Costa-Silva, Bruno

doi:10.1002/1878-0261.12777

Cited by 132 publications

(133 citation statements)

References 86 publications

(111 reference statements)

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“…Microvesicles are formed through pinching off of the plasma membrane and apoptotic bodies are released during apoptosis (Verderio et al, 2014; Yanez‐Mo et al, 2015). EVs also contain proteins, lipids, and nucleic acids that can be delivered to target cells (Elzanowska et al, 2020; Greening et al, 2017; Kim et al, 2017). Recent data indicate that ccf‐mtDNA can be detected in EVs derived from myoblasts, astrocytes and glioblastoma cells grown in vitro and also in plasma EVs from women with hormonal therapy‐resistant breast cancer (Guescini et al, 2010a; Guescini, Guidolin, et al, 2010; Sansone et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial DNA in extracellular vesicles declines with age

et al. 2020

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The mitochondrial free radical theory of aging suggests that accumulating oxidative damage to mitochondria and mitochondrial DNA (mtDNA) plays a central role in aging. Circulating cell‐free mtDNA (ccf‐mtDNA) isolated from blood may be a biomarker of disease. Extracellular vesicles (EVs) are small (30–400 nm), lipid‐bound vesicles capable of shuttling proteins, nucleic acids, and lipids as part of intercellular communication systems. Here, we report that a portion of ccf‐mtDNA in plasma is encapsulated in EVs. To address whether EV mtDNA levels change with human age, we analyzed mtDNA in EVs from individuals aged 30–64 years cross‐sectionally and longitudinally. EV mtDNA levels decreased with age. Furthermore, the maximal mitochondrial respiration of cultured cells was differentially affected by EVs from old and young donors. Our results suggest that plasma mtDNA is present in EVs, that the level of EV‐derived mtDNA is associated with age, and that EVs affect mitochondrial energetics in an EV age‐dependent manner.

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Section: Introductionmentioning

confidence: 99%

“…Microvesicles are formed through pinching off of the plasma membrane and apoptotic bodies are released during apoptosis (Verderio et al, 2014;Yanez-Mo et al, 2015). EVs also contain proteins, lipids, and nucleic acids that can be delivered to target cells (Elzanowska et al, 2020;Greening et al, 2017;Kim et al, 2017).…”

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confidence: 99%

Mitochondrial DNA in extracellular vesicles declines with age

et al. 2020

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“…Evidence indicate that DNA can be transferred from cell-to-cell through extracellular vesicles ( Elzanowska et al, 2020 ). In addition, erythrocytes infected with Plasmodium falciparum can transfer parasite DNA to other infected cells via the release of extracellular vesicles ( Regev-Rudzki et al, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Study on the Occurrence of Genetic Exchange Among Parasites of the Leishmania mexicana Complex

Telittchenko

Descoteaux

2020

Front. Cell. Infect. Microbiol.

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In Leishmania, genetic exchange has been experimentally demonstrated to occur in the sand fly vector and in promastigote axenic cultures through a meiotic-like process. No evidence of genetic exchange in mammalian hosts have been reported so far, possibly due to the fact that the Leishmania species used in previous studies replicate within individual parasitophorous vacuoles. In the present work, we explored the possibility that residing in communal vacuoles may provide conditions favorable for genetic exchange for L. mexicana and L. amazonensis. Using promastigote lines of both species harboring integrated or episomal drug-resistance markers, we assessed whether genetic exchange can occur in axenic cultures, in infected macrophages as well as in infected mice. We obtained evidence of genetic exchange for L. amazonensis in both axenic promastigote cultures and infected macrophages. However, the resulting products of those putative genetic events were unstable as they did not sustain growth in subsequent sub-cultures, precluding further characterization.

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“…Importantly, the pathological state of cell of origin additionally affects molecular composition of released EVs (van Niel et al, 2018). In general, EVs consist of a lipid bilayer membrane that surrounds a small amount of cytosol, and they contain various typical proteins [proteins involved in membrane trafficking, tetraspanins, adhesion molecules, cytoskeletal proteins, endosomal proteins (Kowal et al, 2016;Zhang H. et al, 2018;Théry et al, 2018)], lipids [ceramide, cholesterol, phosphatidylserine (Skotland et al, 2020)], nucleic acids [miRNA, mRNA, and DNA (Elzanowska et al, 2020;O'Brien et al, 2020)] and metabolites (Puhka et al, 2017). In cancer patients, EVs in body fluids were shown to accumulate oncogenes, tumor suppressor genes and their products, signature proteins and RNAs, and mutated genomic DNA (Zocco et al, 2014;An et al, 2015;González and Falcón-Pérez, 2015;Rowland et al, 2019;Vasconcelos et al, 2019;Chennakrishnaiah et al, 2020).…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

“…DNA only recently gained attention as an important constituent of EVs or other extracellular particles and remains poorly understood. EV-DNA varies in its localization and structure (Elzanowska et al, 2020;Malkin and Bratman, 2020). It is attached to the surface or is present in the lumen of EVs and can range in size from 200 bp in small EVs to up to >2 million bp in large EVs.…”

Section: Extracellular Vesiclesmentioning

confidence: 99%

Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

2021

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Biomarkers that can guide cancer therapy based on patients’ individual cancer molecular signature can enable a more effective treatment with fewer adverse events. Data on actionable somatic mutations and germline genetic variants, studied by personalized medicine and pharmacogenomics, can be obtained from tumor tissue or blood samples. As tissue biopsy cannot reflect the heterogeneity of the tumor or its temporal changes, liquid biopsy is a promising alternative approach. In recent years, extracellular vesicles (EVs) have emerged as a potential source of biomarkers in liquid biopsy. EVs are a heterogeneous population of membrane bound particles, which are released from all cells and accumulate into body fluids. They contain various proteins, lipids, nucleic acids (miRNA, mRNA, and DNA) and metabolites. In cancer, EV biomolecular composition and concentration are changed. Tumor EVs can promote the remodeling of the tumor microenvironment and pre-metastatic niche formation, and contribute to transfer of oncogenic potential or drug resistance during chemotherapy. This makes them a promising source of minimally invasive biomarkers. A limited number of clinical studies investigated EVs to monitor cancer progression, tumor evolution or drug resistance and several putative EV-bound protein and RNA biomarkers were identified. This review is focused on EVs as novel biomarker source for personalized medicine and pharmacogenomics in oncology. As several pharmacogenes and genes associated with targeted therapy, chemotherapy or hormonal therapy were already detected in EVs, they might be used for fine-tuning personalized cancer treatment.

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DNA in extracellular vesicles: biological and clinical aspects

Cited by 132 publications

References 86 publications

Mitochondrial DNA in extracellular vesicles declines with age

Mitochondrial DNA in extracellular vesicles declines with age

Study on the Occurrence of Genetic Exchange Among Parasites of the Leishmania mexicana Complex

Extracellular Vesicles: A Novel Tool Facilitating Personalized Medicine and Pharmacogenomics in Oncology

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