Mass spectrometry-based proteome profiling of extracellular vesicles and their roles in cancer biology

Bandu, Raju; Oh, Jae Won; Kim, Kwang Pyo

doi:10.1038/s12276-019-0218-2

Cited by 106 publications

(92 citation statements)

References 109 publications

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“…Recent studies have demonstrated that EV surface proteins bear characteristics of their tissue of origin and these EVs can be captured from bodily fluids using antibody-based assays targeting these proteins [ 29 , 30 ]. Proteomic profiling of EVs is a novel and sensitive approach to increase understanding of EV function and its use has been successful in unravelling their role in cancer [ 31 ]. A proteomic approach will also reveal potential protein biomarkers for isolating tissue-specific EVs.…”

Section: Introductionmentioning

confidence: 99%

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts

et al. 2020

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Background Fibroblasts are the powerhouses responsible for the production and assembly of extracellular matrix (ECM). Their activity needs to be tightly controlled especially within the musculoskeletal system, where changes to ECM composition affect force transmission and mechanical loading that are required for effective movement of the body. Extracellular vesicles (EVs) are a mode of cell-cell communication within and between tissues, which has been largely characterised in cancer. However, it is unclear what the role of healthy fibroblast-derived EVs is during tissue homeostasis. Methods Here, we performed proteomic analysis of small EVs derived from primary human muscle and tendon cells to identify the potential functions of healthy fibroblast-derived EVs. Results Mass spectrometry-based proteomics revealed comprehensive profiles for small EVs released from healthy human fibroblasts from different tissues. We found that fibroblast-derived EVs were more similar than EVs from differentiating myoblasts, but there were significant differences between tendon fibroblast and muscle fibroblast EVs. Small EVs from tendon fibroblasts contained higher levels of proteins that support ECM synthesis, including TGFβ1, and muscle fibroblast EVs contained proteins that support myofiber function and components of the skeletal muscle matrix. Conclusions Our data demonstrates a marked heterogeneity among healthy fibroblast-derived EVs, indicating shared tasks between EVs of skeletal muscle myoblasts and fibroblasts, whereas tendon fibroblast EVs could play a fibrotic role in human tendon tissue. These findings suggest an important role for EVs in tissue homeostasis of both tendon and skeletal muscle in humans.

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Section: Introductionmentioning

confidence: 99%

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts

et al. 2020

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“…Gut microbiota can secrete different types of EVs, including outer membrane vesicles (OMVs), shedding vesicles, and apoptotic bodies 8,9 . EVs are mainly composed of lipids, proteins, nucleic acids, and metabolites [10][11][12] . Although the underlying mechanisms are still unclear, their primary role is to transport active biomolecules into cells over long distances, providing drug delivery to target sites or regulating host cellular responses 11,13 .Recent studies have provided mechanistic evidences for the participation of the gut flora in CRC development.…”

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confidence: 99%

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Kim

Yang

Seo³

et al. 2020

Sci Rep

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Colorectal cancer (CRC) is the most common type cancers in the world. CRC occurs sporadically in the majority of cases, indicating the predominant cause of the disease are environmental factors. Diet-induced changes in gut-microbiome are recently supposed to contribute on epidemics of CRC. This study was aimed to investigate the association of metagenomics and metabolomics in gut extracellular vesicles (EVs) of CRC and healthy subjects. A total of 40 healthy volunteers and 32 patients with CRC were enrolled in this study. Metagenomic profiling by sequencing 16 S rDNA was performed for assessing microbial codiversity. We explored the small molecule metabolites using gas chromatography-time-of-flight mass spectrometry. In total, stool EVs were prepared from 40 healthy volunteers and 32 patients with CRC. Metagenomic profiling demonstrated that bacterial phyla, particularly of Firmicutes and Proteobacteria, were significantly altered in patients with colorectal cancer. Through metabolomics profiling, we determined seven amino acids, four carboxylic acids, and four fatty acids; including short-chain to long chain fatty acids that altered in the disease group. Binary logistic regression was further tested to evaluate the diagnostic performance. In summary, the present findings suggest that gut flora dysbiosis may result in alternation of amino acid metabolism, which may be correlated with the pathogenesis of CRC.Colorectal cancer (CRC) is the most common type cancers in the world 1 . The majority of CRC occurs sporadically, indicating that environmental influences are the predominant cause of the disease 2 . Dietary pattern has long been considered as the most important lifestyle risk factor for CRC. In vivo and in vitro studies have investigated the effect of protein intake on CRC risk and suggest that consumption of excessive protein could lead to DNA damage and influence on the maintenance of colonocyte intergrity 3,4 . Diet-induced changes in gut-microbiome are recently supposed to contribute on epidemics of CRC. Accordingly, studies have suggested that the intestinal microbiome might be important for CRC initiation and progression, since tumors preferentially develop in the distal colon and rectum, which are colonized by approximately 70% of host microbiomes 2,5 . The microbiome has the potential to generate a microenvironment that favors the development of CRC, presumably by recruiting mediators such as interleukins, tumor necrosis factor-alpha, and reactive oxygen species 6,7 . Furthermore, metabolic products of the gut microbiota might increase the risk of developing colorectal cancer. For example, high levels of acetaldehyde produced by the gut microbiota can break down colonial folate, thereby increasing CRC risk 7 .Microbe-derived extracellular vesicles (EVs) are emerging as an important new research subject in understanding the intersection of the gut-microbial communities and human health. Gut microbiota can secrete different types of EVs, including outer membrane vesicles (OMVs), shedding vesicles, and a...

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“…c-MYC activation induces glycolysis which facilitates lactate production (67) and mTOR pathway drives anabolic metabolism (58,59,68). All these oncogenic proteins have been reported in tumor EVs (69) and could be influencing these metabolic pathways in the recipient neighboring glioma cells to favor progression. Recent studies showed that large oncosomes/ large EVs preferentially contain protein cargo targeted to mitochondrial metabolic processes including VDAC1/2, the solute carriers SLC25A6 and SLC25A5 that are mitochondrial ADP/ATP translocators as well as the ATP synthase subunit ATP5B.…”

Section: Glioma Ev Mediated Reprogramming Of Metabolic Activitymentioning

confidence: 99%

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

Yekula

Muralidharan

et al. 2020

Front. Immunol.

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Glioblastomas (GBM) are highly aggressive primary brain tumors. Complex and dynamic tumor microenvironment (TME) plays a crucial role in the sustained growth, proliferation, and invasion of GBM. Several means of intercellular communication have been documented between glioma cells and the TME, including growth factors, cytokines, chemokines as well as extracellular vesicles (EVs). EVs carry functional genomic and proteomic cargo from their parental cells and deliver that information to surrounding and distant recipient cells to modulate their behavior. EVs are emerging as crucial mediators of establishment and maintenance of the tumor by modulating the TME into a tumor promoting system. Herein we review recent literature in the context of GBM TME and the means by which EVs modulate tumor proliferation, reprogram metabolic activity, induce angiogenesis, escape immune surveillance, acquire drug resistance and undergo invasion. Understanding the multifaceted roles of EVs in the niche of GBM TME will provide invaluable insights into understanding the biology of GBM and provide functional insights into the dynamic EV-mediated intercellular communication during gliomagenesis, creating new opportunities for GBM diagnostics and therapeutics.

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Mass spectrometry-based proteome profiling of extracellular vesicles and their roles in cancer biology

Cited by 106 publications

References 109 publications

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts

Proteomics identifies differences in fibrotic potential of extracellular vesicles from human tendon and muscle fibroblasts

Colorectal cancer diagnostic model utilizing metagenomic and metabolomic data of stool microbial extracellular vesicles

Extracellular Vesicles in Glioblastoma Tumor Microenvironment

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