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Aug 23, 2016

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EV literature (RSS feed from PubMed)

Search terms: exosomes OR "extracellular vesicles" OR microvesicles OR microparticles. Direct link to the PubMed search here.

Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics.

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Comparison of exosomes and ferritin protein nanocages for the delivery of membrane protein therapeutics.

J Control Release. 2018 Apr 18;:

Authors: Cho E, Nam GH, Hong Y, Kim YK, Kim DH, Yang Y, Kim IS

Abstract
Exosomes are small membrane vesicles secreted by most cell types that play an important role in intercellular communication. Due to the characteristic of transferring their biomacromolecules, exosomes have potential as a new alternative for delivering protein therapeutics. Here, we investigate whether exosomes provide crucial advantages over other nanoparticles, in particular protein nanocage formulations, as a delivery system for membrane protein therapeutics. We characterized membrane-scaffold-based exosomes and protein-scaffold-based ferritin nanocages, both harboring SIRPα (signal regulatory protein α), an antagonist of CD47 on tumor cells. The efficacy of these two systems in delivering protein therapeutics was compared by testing their ability to enhance phagocytosis of tumor cells by bone-marrow-derived macrophages and subsequent inhibition of in vivo tumor growth. These analyses allowed us to comprehensively conclude that the therapeutic index of exosome-mediated CD47 blockade against tumor growth inhibition was higher than that of the same dose of ferritin-SIRPα. The results of this analysis reveal the importance of the unique characteristics of exosomes, in particular their membrane scaffold, in improving therapeutic protein delivery compared with protein-scaffold-based nanocages.

PMID: 29679665 [PubMed - as supplied by publisher]

Activation of TLR3 and its adaptor TICAM-1 increases miR-21 levels in extracellular vesicles released from human cells.

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Activation of TLR3 and its adaptor TICAM-1 increases miR-21 levels in extracellular vesicles released from human cells.

Biochem Biophys Res Commun. 2018 Apr 18;:

Authors: Fukushima Y, Okamoto M, Ishikawa K, Kouwaki T, Tsukamoto H, Oshiumi H

Abstract
Pattern-recognition receptors (PRRs) recognizes viral RNAs and trigger the innate immune responses. Toll-like receptor 3 (TLR3), a PRR, recognizes viral double-stranded RNA (dsRNA) in endolysosomes, whereas cytoplasmic dsRNA is sensed by another PRR, MDA5. TLR3 and MDA5 utilize TICAM-1 and MAVS, respectively, to trigger the signal for inducing innate immune responses. Extracellular vesicles (EVs) include the exosomes and microvesicles; an accumulating body of evidence has shown that EVs delivers functional RNA, such as microRNAs (miRNAs), to other cells and thus mediate intercellular communications. Therefore, EVs carrying miRNAs affect innate immune responses in macrophages and dendritic cells. However, the mechanism underlying the regulation of miRNA levels in EVs remains unclear. To elucidate the mechanism, we sought to reveal the pathway that control miRNA expression levels in EVs. Here, we found that TLR3 stimulation increased miR-21 levels in EVs released from various types of human cells. Ectopic expression of the TLR3 adaptor, TICAM-1, increased miR-21 levels in EVs but not intracellular miR-21 levels, suggesting that TICAM-1 augmented sorting of miR-21 to EVs. In contrast, the MDA5 adaptor, MAVS, did not increase miR-21 levels in EVs. The siRNA for TICAM-1 reduced EV miR-21 levels after stimulation of TLR3. Collectively, our data indicate a novel role of the TLR3-TICAM-1 pathway in controlling miR-21 levels in EVs.

PMID: 29679565 [PubMed - as supplied by publisher]

Slow Release of HIV-1 Protein Nef from Vesicle-like Structures Is Inhibited by Cytosolic Calcium Elevation in Single Human Microglia.

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Slow Release of HIV-1 Protein Nef from Vesicle-like Structures Is Inhibited by Cytosolic Calcium Elevation in Single Human Microglia.

Mol Neurobiol. 2018 Apr 21;:

Authors: Stenovec M, Lasič E, Dominkuš PP, Bobnar ST, Zorec R, Lenassi M, Kreft M

Abstract
Once infected by HIV-1, microglia abundantly produce accessory protein Nef that enhances virus production and infectivity, but little is known about its intracellular compartmentalization, trafficking mode(s), and release from microglia. Here, we transfected immortalized human microglia with a plasmid encoding Nef tagged with green fluorescent protein (Nef.GFP) to biochemically and microscopically identify Nef.GFP-associated cellular compartments and examine their mobility and Nef release from cultured cells. Immunoblotting revealed that Nef.GFP confined to subcellular fractions with a buoyant density similar to organelles positive for lysosomal-associated membrane protein 1 (LAMP1) but structurally segregated from dextran-laden and LysoTracker-laden endo-/lysosomes in live cells. As revealed by confocal microscopy, Nef.GFP-positive vesicle-like structures were smaller than dextran-laden vesicles and displayed slow and non-directional mobility, in contrast to the faster and directional mobility of dextran-laden vesicles. Ionomycin-evoked elevation in intracellular free Ca2+ concentration ([Ca2+] i ) negligibly affected mobility of Nef.GFP structures but strongly and irrecoverably attenuated mobility of dextran-laden vesicles. A slow time-dependent decrease in the number of Nef.GFP-positive structures was observed in non-stimulated controls (5 ± 1 structures/min), but not in ionomycin-stimulated cells (0 ± 2 structures/min; P < 0.05), indicating that elevated [Ca2+] i inhibits the release of Nef.GFP structures. The latter significantly co-localized with membrane sites immunopositive for the tetraspanins CD9 (36 ± 4%) and CD81 (22 ± 1%). This is the first report to demonstrate that microglial CD9- and CD81-positive plasma membrane-derived compartments are associated with biogenesis and Nef release.

PMID: 29679260 [PubMed - as supplied by publisher]

Extracellular vesicles and their content in bioactive lipid mediators: more than a sack of microRNA.

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Extracellular vesicles and their content in bioactive lipid mediators: more than a sack of microRNA.

J Lipid Res. 2018 Apr 20;:

Authors: Boilard E

Abstract
Extracellular vesicles (EVs), such as exosomes and microvesicles, are small membrane-bound vesicles released by cells under various conditions. In a multitude of physiological and pathological conditions, EVs contribute to intercellular communication by facilitating exchange of material between cells. Rapidly growing interest is aimed at better understanding EV function and their use as biomarkers. The vast EV cargo includes cytokines, growth factors, organelles, nucleic acids (messenger and micro RNA), and transcription factors. A large proportion of research dedicated to EVs is focused on their microRNA cargo; however, much less is known about other EV constituents, in particular eicosanoids. These potent bioactive lipid mediators, derived from arachidonic acid, are shuttled in EVs along with the enzymes in charge of their synthesis. In the extracellular milieu, EVs also interact with secreted phospholipases to generate eicosanoids, which then regulate the transfer of cargo into a cellular recipient. Eicosanoids are useful as biomarkers and contribute to a variety of biological functions, including modulation of distal immune responses. Here, we review the reported roles of eicosanoids conveyed by EVs and describe their potential as biomarker.

PMID: 29678959 [PubMed - as supplied by publisher]

Cholesterol and the journey of extracellular vesicles.

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Cholesterol and the journey of extracellular vesicles.

J Lipid Res. 2018 Apr 20;:

Authors: Pfrieger FW, Vitale N

Abstract
Eukaryotic cells employ distinct means to release specific signals and material. Research within the last decade has identified different types of membrane-enclosed structures collectively called extracellular vesicles (EVs) as one of them. EVs fall in two categories depending on their subcellular origin. Exosomes are generated within the endosomal system and reach the extracellular space upon fusion of multivesicular bodies (MVBs). Microvesicles or microparticles are generated by shedding of the plasma membrane. Sterols are essential components of eukaryotic membranes and serve as precursors or cofactors of numerous signaling molecules; their content and subcellular distribution are tightly controlled. The prominent roles of sterols in cells raise the question whether and how these components impact EVs. In this review we compile evidence for cholesterol accumulation in EVs and discuss its possible contribution to their biogenesis, release and uptake. We also consider potential implications of EVs in cellular sterol homeostasis and in cholesterol-related diseases.

PMID: 29678958 [PubMed - as supplied by publisher]

A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite.

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A new role for extracellular vesicles: how small vesicles can feed tumors' big appetite.

J Lipid Res. 2018 Apr 20;:

Authors: Lazar I, Clement E, Attane C, Muller C, Nieto L

Abstract
Cancer cells must adapt their metabolism in order to meet the energy requirements for cell proliferation, survival in nutrient-deprived environments and dissemination. In particular, fatty acid metabolism is emerging as a critical process for tumors. Fatty acid metabolism can be modulated through intrinsic changes in gene expression or signaling between tumor cells, but also in response to signals from the surrounding microenvironment. Among these signals, extracellular vesicles could play an important role in fatty acid metabolism remodeling. In this review, we will present the role of extracellular vesicles in tumor progression and especially in metabolic reprogramming. Particular attention will be granted to adipocytes. These cells, which are specialized in storing and releasing FAs, are able to shift tumor metabolism towards the use of fatty acids and, subsequently, increase tumor aggressiveness. Recent work demonstrates the involvement of extracellular vesicles in this metabolic symbiosis.

PMID: 29678957 [PubMed - as supplied by publisher]

Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment.

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Emerging role of exosome-derived long non-coding RNAs in tumor microenvironment.

Mol Cancer. 2018 Apr 20;17(1):82

Authors: Sun Z, Yang S, Zhou Q, Wang G, Song J, Li Z, Zhang Z, Xu J, Xia K, Chang Y, Liu J, Yuan W

Abstract
Exosomes are extracellular vesicles released by many cell types and have been attributed for their roles in many diseases including cancer. Exosomes secreted by tumor cells and stromal cells are critical mediators of intercellular communication in tumor microenvironments. Long noncoding RNAs (lncRNAs) are selectively sorted into exosomes and can regulate cancer onset and progression in a variety of ways. In this review, we summarize the characteristics of exosomal lncRNAs and their dysregulation in multiple types of cancer. We provide an overview of current research on exosomal lncRNAs in tumor microenvironments, especially the functions of exosomal lncRNAs in regulating tumor biology. A deeper understanding of the role of exosomal lncRNAs in the tumor microenvironment may help provide new diagnostic and prognostic markers for cancer.

PMID: 29678180 [PubMed - in process]

 

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