Biogenesis and Functions of Exosomes and Extracellular Vesicles

Dreyer, Florian S.; Baur, Andreas S.

doi:10.1007/978-1-4939-3753-0_15

Cited by 118 publications

(99 citation statements)

References 80 publications

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“…A multitude of different effects of exosomes was reported. In cancer, exosomes reprogram tissue to allow growth of metastases, act as decoys to escape the immune system, or spread factors conferring resistance to drugs used in chemotherapy (Chiarugi & Cirri, 2016; Desrochers et al, 2016; Dorsam, Reiners, & von Strandmann, 2018; Dreyer & Baur, 2016; Kahlert & Kalluri, 2013; Kalluri, 2016; Ruivo, Adem, Silva, & Melo, 2017; S, Mager, Breakefield, & Wood, 2013; M. Silva & Melo, 2015; Steinbichler, Dudas, Riechelmann, & Skvortsova, 2017; Weidle, Birzele, Kollmorgen, & Ruger, 2017; H.…”

Section: Got Exosomes: What’s (Really) In Your Prep?mentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

118

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Exosomes are secreted extracellular vesicles (EVs) that carry micro RNAs and other factors to reprogram cancer cells and tissues affected by cancer. Exosomes are exchanged between cancer cells and other tissues, often to prepare a premetastatic niche, escape immune surveillance, or spread multidrug resistance. Only a few studies investigated the function of lipids in exosomes, although their lipid composition is different from that of the secreting cells. Ceramide is one of the lipids critical for exosome formation and it is also enriched in these EVs. New research suggests that lipids in the exosomal membrane may organize and transmit “mobile rafts” that turn exosomes into extracellular signalosomes spreading activation of cell signaling pathways in oncogenesis and metastasis. Ceramide may modulate the function of mobile rafts and their effect on these cell signaling pathways. The critical role of lipids and in particular, ceramide for formation, secretion, and function of exosomes may lead to a radically new understanding of cancer biology and therapy.

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Section: Got Exosomes: What’s (Really) In Your Prep?mentioning

confidence: 99%

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Elsherbini

Bieberich

2018

Advances in Cancer Research

118

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“…Extracellular vesicles (EV) are released not only from different mammalian cell-types but also from microorganisms and parasites and have the capacity to transfer complex biological information12345. Various types of EV ranging in size from 20 nm to 1,000 nm in diameter have been described and are classified mainly on their mechanisms of biogenesis and their physiological functions16.…”

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confidence: 99%

“…Various types of EV ranging in size from 20 nm to 1,000 nm in diameter have been described and are classified mainly on their mechanisms of biogenesis and their physiological functions16. Those designated exosomes are nanosized vesicles of 50–100 nm which are released extracellularly after fusion of multicellular endosomes with the cell membrane, whereas microvesicles (MV) are larger vesicles (100–1,000 nm) generated through outward budding of the plasma membrane15. Gram-negative bacteria produce MV by outward budding of the outer membrane and these vesicles are therefore referred to as outer membrane vesicles (OMV) with a diameter in the range of 20–500 nm6.…”

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confidence: 99%

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Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

Rayner

Bruhn

Vallhov

et al. 2017

Sci Rep

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Malassezia is the dominant fungus in the human skin mycobiome and is associated with common skin disorders including atopic eczema (AE)/dermatitis. Recently, it was found that Malassezia sympodialis secretes nanosized exosome-like vesicles, designated MalaEx, that carry allergens and can induce inflammatory cytokine responses. Extracellular vesicles from different cell-types including fungi have been found to deliver functional RNAs to recipient cells. In this study we assessed the presence of small RNAs in MalaEx and addressed if the levels of these RNAs differ when M. sympodialis is cultured at normal human skin pH versus the elevated pH present on the skin of patients with AE. The total number and the protein concentration of the released MalaEx harvested after 48 h culture did not differ significantly between the two pH conditions nor did the size of the vesicles. From small RNA sequence data, we identified a set of reads with well-defined start and stop positions, in a length range of 16 to 22 nucleotides consistently present in the MalaEx. The levels of small RNAs were not significantly differentially expressed between the two different pH conditions indicating that they are not influenced by the elevated pH level observed on the AE skin.Extracellular vesicles (EV) are released not only from different mammalian cell-types but also from microorganisms and parasites and have the capacity to transfer complex biological information [1][2][3][4][5] . Various types of EV ranging in size from 20 nm to 1,000 nm in diameter have been described and are classified mainly on their mechanisms of biogenesis and their physiological functions 1,6 . Those designated exosomes are nanosized vesicles of 50-100 nm which are released extracellularly after fusion of multicellular endosomes with the cell membrane, whereas microvesicles (MV) are larger vesicles (100-1,000 nm) generated through outward budding of the plasma membrane 1,5 . Gram-negative bacteria produce MV by outward budding of the outer membrane and these vesicles are therefore referred to as outer membrane vesicles (OMV) with a diameter in the range of 20-500 nm 6 . Exosomes can be detected in body fluids such as urine, bronchoalveolar lavage fluid (BAL), breast milk and serum 7 . The functions of exosomes include immunoregulatory mechanisms such as modulation of antigen presentation, immune activation, immune suppression, immune surveillance and intercellular communication 6 . EV from microorganisms with thick cell walls, such as Gram-positive bacteria and fungi, have been associated with cytotoxicity, the invasion of host cells, and the transfer of virulence factors 2 . As seen with exosomes 1,8 , fungal EV have been observed to deliver functional messenger (m)RNAs and micro (mi)RNA-like RNAs to recipient cells 9,10 . miRNAs are small non-coding RNAs with a length between 20 and 22 nucleotides (nt) 11 . They are spliced from precursor sequences that form the stable hairpin necessary for transportation from the nucleus to the cytoplasm. After the miRNA has been c...

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“…After their release into the extracellular environment, exosomes can bind recipient cells to transfer their content. A variety of biomolecules, such as lipids, proteins, and nucleic acids (mRNA, microRNA, and DNA) are present in exosomes and can regulate the biological activity of recipient cells (7–10). …”

Section: Introductionmentioning

confidence: 99%

HCV-E2 inhibits hepatocellular carcinoma metastasis by stimulating mast cells to secrete exosomal shuttle microRNAs

Zhen

et al. 2017

Oncology Letters

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Exosomal miRNAs are emerging as mediators of the interaction between mast cells (MCs) and tumor cells. The exosomal miRNAs can be internalized by liver cancer cells to inhibit cell metastasis. We explored the interaction between MCs and hepatocellular carcinoma (HCC) cells. We used hepatitis C virus E2 envelope glycoprotein (HCV-E2) to stimulate MCs and harvest MCs-derived exosomes to detect the miRNAs and changes of exosomal miRNAs before and after stimulation. Through miRNA microarray analysis, we identified 19 differentially expressed miRNAs in exosomes derived from MCs with or without HCV-E2 treatment. HCV-E2 not only increased the level of miRNA-490 in MCs and their secreted exosomes but also increased the levels of miRNA-490 in recipient HepG2 cells, which ultimately inhibited the ERK1/2 pathway. The transfection of antagomiR-490 significantly decreased the levels of miR-490 in MCs, MCs-derived exosomes, and recipient HepG2 cells and increased migration of HepG2, indicating that miR-490 is involved in the regulation of HepG2 cell migration. The present study suggests that MCs can inhibit HCC cell metastasis by inhibiting the ERK1/2 pathway by transferring the exosomal shuttle microRNAs into HCC cells, which provides new insights for the biological therapy of HCC induced by hepatitis C.

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Biogenesis and Functions of Exosomes and Extracellular Vesicles

Cited by 118 publications

References 80 publications

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Ceramide and Exosomes: A Novel Target in Cancer Biology and Therapy

Identification of small RNAs in extracellular vesicles from the commensal yeast Malassezia sympodialis

HCV-E2 inhibits hepatocellular carcinoma metastasis by stimulating mast cells to secrete exosomal shuttle microRNAs

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