Role of exosomes and microvesicles in hypoxia‐associated tumour development and cardiovascular disease

Belting, Mattias; Christianson, Helena C.

doi:10.1111/joim.12393

Cited by 46 publications

(35 citation statements)

References 115 publications

(173 reference statements)

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“…In addition, EVs may be altered in number and composition in several conditions [6–9], and they have emerging as potential biomarkers of diagnosis and prognosis [10]. To date, there are no published reports of EVs isolation and characterisation in CFS/ME.…”

Section: Introductionmentioning

confidence: 99%

Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

Castro-Marrero

Serrano-Pertierra

Oliveira-Rodríguez

et al. 2018

J of Extracellular Vesicle

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Chronic Fatigue Syndrome (CFS), also known as Myalgic Encephalomyelitis (ME) is an acquired, complex and multisystem condition of unknown etiology, no established diagnostic lab tests and no universally FDA-approved drugs for treatment. CFS/ME is characterised by unexplicable disabling fatigue and is often also associated with numerous core symptoms. A growing body of evidence suggests that extracellular vesicles (EVs) play a role in cell-to-cell communication, and are involved in both physiological and pathological processes. To date, no data on EV biology in CFS/ME are as yet available. The aim of this study was to isolate and characterise blood-derived EVs in CFS/ME. Blood samples were collected from 10 Spanish CFS/ME patients and 5 matched healthy controls (HCs), and EVs were isolated from the serum using a polymer-based method. Their protein cargo, size distribution and concentration were measured by Western blot and nanoparticle tracking analysis. Furthermore, EVs were detected using a lateral flow immunoassay based on biomarkers CD9 and CD63. We found that the amount of EV-enriched fraction was significantly higher in CFS/ME subjects than in HCs (p = 0.007) and that EVs were significantly smaller in CFS/ME patients (p = 0.014). Circulating EVs could be an emerging tool for biomedical research in CFS/ME. These findings provide preliminary evidence that blood-derived EVs may distinguish CFS/ME patients from HCs. This will allow offer new opportunities and also may open a new door to identifying novel potential biomarkers and therapeutic approaches for the condition.

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Section: Introductionmentioning

confidence: 99%

Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

Castro-Marrero

Serrano-Pertierra

Oliveira-Rodríguez

et al. 2018

J of Extracellular Vesicle

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“…They have been shown to transfer RNAs and proteins that are functional in the recipient cells (15,16). They can be found in various body fluids and in the tumour microenvironment and can transmit messages to neighbouring cells as well as to distant cells (17,18). miRNAs, short non-coding RNAs whose levels can be altered during stress response (19), can also be shuttled between cells in the tumour microenvironment via EVs.…”

mentioning

confidence: 99%

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

Samuel

Mulcahy

Furlong

et al. 2017

Phil. Trans. R. Soc. B

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Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients. This article is part of the discussion meeting issue ‘Extracellular vesicles and the tumour microenvironment’.

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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.…”

mentioning

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.…”

mentioning

confidence: 99%

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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Role of exosomes and microvesicles in hypoxia‐associated tumour development and cardiovascular disease

Cited by 46 publications

References 115 publications

Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

Circulating extracellular vesicles as potential biomarkers in chronic fatigue syndrome/myalgic encephalomyelitis: an exploratory pilot study

Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells

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

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