Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake

Abels, Erik R.; Breakefield, Xandra O.

doi:10.1007/s10571-016-0366-z

Cited by 1,300 publications

(1,310 citation statements)

References 133 publications

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“…However, very little is currently known about the mechanisms that cells adopt to internalize EVs larger than Exo (25). We exposed immortalized WPMY-1 myofibroblasts to LO labeled with the fluorescent dye PKH26 and quantitatively analyzed LO uptake by flow cytometry.…”

Section: Lo Are Internalized By Heterologous Cellsmentioning

confidence: 99%

MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer

et al. 2017

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Communication between cancer cells and the tumor microenvironment results in the modulation of complex signaling networks that facilitate tumor progression. Here, we describe a new mechanism of intercellular communication originating from large oncosomes (LO), which are cancer cell-derived, atypically large (1-10 mm) extracellular vesicles (EV). We demonstrate that, in the context of prostate cancer, LO harbor sustained AKT1 kinase activity, nominating them as active signaling platforms. Active AKT1 was detected in circulating EV from the plasma of metastatic prostate cancer patients and was LO specific. LO internalization induced reprogramming of human normal prostate fibroblasts as reflected by high levels of a-SMA, IL6, and MMP9. In turn, LO-reprogrammed normal prostate fibroblasts stimulated endothelial tube formation in vitro and promoted tumor growth in mice. Activation of stromal MYC was critical for this reprogramming and for the sustained cellular responses elicited by LO, both in vitro and in vivo in an AKT1-dependent manner. Inhibition of LO internalization prevented activation of MYC and impaired the tumor-supporting properties of fibroblasts. Overall, our data show that prostate cancer-derived LO powerfully promote establishment of a tumor-supportive environment by inducing a novel reprogramming of the stroma. This mechanism offers potential alternative options for patient treatment. Cancer Res; 77(9); 2306-17.Ó2017 AACR.

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Section: Lo Are Internalized By Heterologous Cellsmentioning

confidence: 99%

MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer

et al. 2017

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“…Furthermore, although extracellular RNAs have been detected in mammals, their biology is not well-understood and is under intense investigation (see ref. 52 for a recent review). Using genetic mutants and fluorescently labeled RNAs to control and follow the traffic of extracellular RNAs, our results demonstrate their direct transfer between generations in an animal-an inheritance that can potentially vary based on parental experience.…”

Section: Rnas In Circulation As Carriers Of Gene-specific Informationmentioning

confidence: 99%

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Marre

Traver

Jose

2016

Proc. Natl. Acad. Sci. U.S.A.

107

144

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Experiences during the lifetime of an animal have been proposed to have consequences for subsequent generations. Although it is unclear how such intergenerational transfer of information occurs, RNAs found extracellularly in animals are candidate molecules that can transfer gene-specific regulatory information from one generation to the next because they can enter cells and regulate gene expression. In support of this idea, when double-stranded RNA (dsRNA) is introduced into some animals, the dsRNA can silence genes of matching sequence and the silencing can persist in progeny. Such persistent gene silencing is thought to result from sequencespecific interaction of the RNA within parents to generate chromatin modifications, DNA methylation, and/or secondary RNAs, which are then inherited by progeny. Here, we show that dsRNA can be directly transferred between generations in the worm Caenorhabditis elegans. Intergenerational transfer of dsRNA occurs even in animals that lack any DNA of matching sequence, and dsRNA that reaches progeny can spread between cells to cause gene silencing. Surprisingly, extracellular dsRNA can also reach progeny without entry into the cytosol, presumably within intracellular vesicles. Fluorescently labeled dsRNA is imported from extracellular space into oocytes along with yolk and accumulates in punctate structures within embryos. Subsequent entry into the cytosol of early embryos causes gene silencing in progeny. These results demonstrate the transport of extracellular RNA from one generation to the next to regulate gene expression in an animal and thus suggest a mechanism for the transmission of experience-dependent effects between generations.circulating RNA | parental RNAi | epigenetics | transgenerational inheritance | endocytosis

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“…While EV nomenclature is still controversial (Gould and Raposo 2013), it is generally recognized that there are three major EV subtypes. The first subtype, exosomes, is formed by inward budding of the endosomal membrane to form intraluminal vesicles, and subsequently released to the extracellular space by fusion of multivesicular endosomes (MVE) with the plasma membrane (Abels and Breakefield 2016). The second subtype, commonly referred to as microvesicles (or microparticles or ectosomes), arises by outward budding of the plasma membrane (Abels and Breakefield 2016).…”

Section: Heterogeneity Of Extracellular Vesiclesmentioning

confidence: 99%

“…The first subtype, exosomes, is formed by inward budding of the endosomal membrane to form intraluminal vesicles, and subsequently released to the extracellular space by fusion of multivesicular endosomes (MVE) with the plasma membrane (Abels and Breakefield 2016). The second subtype, commonly referred to as microvesicles (or microparticles or ectosomes), arises by outward budding of the plasma membrane (Abels and Breakefield 2016). The third EV type is apoptotic bodies, large membrane vesicles that are formed by apoptotic membrane blebbing and that contain DNA fragments and cellular organelles (Thery, Ostrowski, and Segura 2009).…”

Section: Heterogeneity Of Extracellular Vesiclesmentioning

confidence: 99%

Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

Benedikter

Wouters

Savelkoul

et al. 2018

Journal of Toxicology and Environmental Health, Part B

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Extracellular vesicles (EV) are secreted signaling entities that enhance various pathological processes when released in response to cellular stresses. Respiratory exposures such as cigarette smoke and air pollution exert cellular stresses and are associated with an increased risk of several chronic diseases. The aim of this review was to examine the evidence that modifications in EV contribute to respiratory exposure-associated diseases. Publications were searched using PubMed and Google Scholar with the search terms (cigarette smoke OR tobacco smoke OR air pollution OR particulate matter) AND (extracellular vesicles OR exosomes OR microvesicles OR microparticles OR ectosomes). All original research articles were included and reviewed. Fifty articles were identified, most of which investigated the effect of respiratory exposures on EV release in vitro (25) and/or on circulating EV in human plasma (24). The majority of studies based their main observations on the relatively insensitive scatter-based flow cytometry of EV (29). EV induced by respiratory exposures were found to modulate inflammation (19), thrombosis (13), endothelial dysfunction (11), tissue remodeling (6), and angiogenesis (3). By influencing these processes, EV may play a key role in the development of cardiovascular diseases and chronic obstructive pulmonary disease and possibly lung cancer and allergic asthma. The current findings warrant additional research with improved methodologies to evaluate the contribution of respiratory exposure-induced EV to disease etiology, as well as their potential as biomarkers of exposure or risk and as novel targets for preventive or therapeutic strategies.

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Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake

Cited by 1,300 publications

References 133 publications

MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer

MYC Mediates Large Oncosome-Induced Fibroblast Reprogramming in Prostate Cancer

Extracellular RNA is transported from one generation to the next in Caenorhabditis elegans

Extracellular vesicles released in response to respiratory exposures: implications for chronic disease

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