Metabolome of Exosomes: Focus on Vesicles Released by Cancer Cells and Present in Human Body Fluids

Zebrowska, Aneta; Skowronek, Agata; Wojakowska, Anna; Widłak, Piotr; Pietrowska, Monika

doi:10.3390/ijms20143461

Cited by 73 publications

(49 citation statements)

References 101 publications

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“…If we consider that metabolites represent an intermediate or end point of any cellular process, they can reflect the phenotype printout of a cell at a specific moment. Thus, monitoring metabolic changes in any biological fluid under a variety of physiological or pathological conditions may be seen as the goldmine of biomarkers of health condition [13]. Moreover, determining the metabolite composition of EVs can reveal important aspects in cell-to-cell communication.…”

Section: Introductionmentioning

confidence: 99%

Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

Gatien

Mermillod

Tsikis

et al. 2019

IJMS

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Oviductal extracellular vesicles (oEVs) have been proposed as key modulators of gamete/embryo maternal interactions. The aim of this study was to examine the metabolite content of oEVs and its regulation across the estrous cycle in cattle. Oviductal EVs were isolated from bovine oviducts ipsilateral and contralateral to ovulation at four stages of the estrous cycle (post-ovulatory stage, early and late luteal phases, and pre-ovulatory stage). The metabolomic profiling of EVs was performed by proton nuclear magnetic resonance spectroscopy (NMR). NMR identified 22 metabolites in oEVs, among which 15 were quantified. Lactate, myoinositol, and glycine were the most abundant metabolites throughout the estrous cycle. The side relative to ovulation had no effect on the oEVs' metabolite concentrations. However, levels of glucose-1-phosphate and maltose were greatly affected by the cycle stage, showing up to 100-fold higher levels at the luteal phase than at the peri-ovulatory phases. In contrast, levels of methionine were significantly higher at peri-ovulatory phases than at the late-luteal phase. Quantitative enrichment analyses of oEV-metabolites across the cycle evidenced several significantly regulated metabolic pathways related to sucrose, glucose, and lactose metabolism. This study provides the first metabolomic characterization of oEVs, increasing our understanding of the potential role of oEVs in promoting fertilization and early embryo development.

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Section: Introductionmentioning

confidence: 99%

Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

Gatien

Mermillod

Tsikis

et al. 2019

IJMS

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“…However, their metabolite compartment is less characterized compared to proteome or miRNome [20]. Here we compared metabolite pro les of whole human serum and serum-derived exosomes and found signi cantly fewer compounds in the latter specimen.…”

Section: Discussionmentioning

confidence: 84%

“…Exosomes are virus-sized (50-150 nm) vesicles of endosomal origin released by the majority of cell types, either normal and cancerous [19]. Exosomes and other classes of extracellular vesicles (EVs) play an essential role in cancer biology being the key mediators of communication between cells [20,21]. EVs present in the blood and other bio uids represent an interesting type of so-called liquid biopsy, which is an emerging source of potential biomarkers [22,23].…”

Section: Introductionmentioning

confidence: 99%

“…There is growing evidence for the increased level of EVs in bio uids of cancer patients as well as radiation-induced enhancement of exosome secretion [24,25]. However, though literature data support the important role of transcriptome and proteome content of cancer-related EVs, much less is known about their metabolome component [20]. Similarly, the data regarding radiationinduced changes in the EVs cargo refer mainly to its transcriptome and proteome [26,27].…”

Section: Introductionmentioning

confidence: 99%

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Metabolic profiles of whole serum and serum-derived exosomes are different in head and neck cancer patients treated by radiotherapy

Wojakowska

Zebrowska

Skowronek

et al. 2020

Preprint

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Background Serum metabolome reflects a general patient's body response to both disease state (e.g., cancer) and implemented treatment (e.g., radiotherapy, RT). Though serum-derived exosomes are an emerging type of liquid biopsy, a metabolite content of these vesicles remains under-researched yet. In this pilot study, we aimed to compare metabolite profiles of the whole serum and serum-derived exosomes in the context of differences between cancer patients and healthy controls as well as patients’ response to RT. Methods Serum samples were collected from 10 healthy volunteers and 10 patients with head and neck cancer, in the latter group samples were taken before and after the end of RT. Exosomes were isolated from serum by the size-exclusion chromatography. Metabolites were purified from the complete serum and exosomes using a methanol extraction and analyzed by the gas chromatography-mass spectrometry (GC-MS). Results An untargeted GC-MS-based approach allowed the detection of 182 and 46 metabolites in serum and exosomes, respectively (33 compounds were present in both types of specimens). The unsupervised analyses revealed that metabolite profiles of the whole serum but not serum-derived exosomes enabled the separation of all 3 groups of samples. There were 27 compounds whose serum levels were markedly different (large effect size) between control and cancer samples and 12 compounds whose serum levels were markedly different between cancer pre-RT and post-RT samples. On the other hand, only 4 metabolites present in exosomes showed markedly different levels between cancer and control samples. Noteworthy, metabolites that differentiated cancer and control samples, either serum or exosomes, were associated with energy metabolism pathways. Serum metabolites affected by RT were associated with pathways involved in the metabolism of amino acids, sugars, lipids, and nucleotides. Conclusions Metabolite profile of serum-derived exosomes is less complex than that of the complete serum. However, cancer-specific features of energy metabolism could be detected in both types of specimens. On the other hand, in contrast to RT-induced changes observed in serum metabolome, this pilot study did not reveal a specific radiation-related pattern of exosome metabolites.

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“…cargoes such as nucleic acids, proteins, and lipids [6][7][8]. EVs are currently classified into different subtypes according to their size, biogenesis mechanisms, cargoes, and so on [9]. They include larger EVs (LEVs) such as shed microvesicles (100-1,000 nm) from the cell membrane, [7] and SEVs which include exosomes (50 -150 nm), secreted from endocytic pathways [10,11].…”

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confidence: 99%

Inhibition of a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

Altei

Pachane

Santos

et al. 2020

Preprint

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Background: Extracellular vesicles (EVs) are lipid-bound particles that are naturally released from cells and mediate cell-cell communication. Integrin adhesion receptors are enriched in small EVs (SEVs) and SEV-carried integrins have been shown to promote cancer cell migration and to mediate organ-specific metastasis; however, how integrins mediate these effects is not entirely clear and could represent a combination of EV binding to extracellular matrix and cells.Methods: To probe integrin role in EVs binding and uptake, we employed a disintegrin inhibitor (DisBa-01) of integrin binding with specificity for avb3 integrin. EVs were purified from MDA-MB-231 cells conditioned media by serial centrifugation method. Isolated EVs were characterized by different techniques and further employed in adhesion, uptake and co-culture experiments.Results: We find that SEVs secreted from MDA-MB-231 breast cancer cells carry avb3 integrin and bind directly to fibronectin-coated plates, which is inhibited by DisBa-01. SEV coating on tissue culture plates also induces adhesion of MDA-MB-231 cells, which is inhibited by DisBa-01 treatment. Analysis of EV uptake and interchange between cells reveals that the amount of CD63-positive EVs delivered from malignant MDA-MB-231 breast cells to non-malignant MCF10A breast epithelial cells is reduced by DisBa-01 treatment. Inhibition of avb3 integrin decreases CD63 expression in cancer cells suggesting an effect on SEV content.Conclusion: In summary, our findings demonstrate for the first time a key role of avb3 integrin in cell-cell communication through SEVs.

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Metabolome of Exosomes: Focus on Vesicles Released by Cancer Cells and Present in Human Body Fluids

Cited by 73 publications

References 101 publications

Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

Metabolomic Profile of Oviductal Extracellular Vesicles across the Estrous Cycle in Cattle

Metabolic profiles of whole serum and serum-derived exosomes are different in head and neck cancer patients treated by radiotherapy

Inhibition of a v b 3 integrin impairs adhesion and uptake of tumor-derived small extracellular vesicles

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