Exosome cargo reflects TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) status in A549 human lung adenocarcinoma cells

Kim, Jiyeon; Kim, Tae Yeon; Lee, Myung‐Shin; Mun, Ji Young; Ihm, Chunhwa; Kim, Soon Ae

doi:10.1016/j.bbrc.2016.07.124

Cited by 104 publications

(85 citation statements)

References 22 publications

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“…A previous study reported that TGF‐β influences microRNA (miRNA) expression in exosomes; however, the role of TGF‐β in promoting exosomal lncRNA expression has not been reported. Here, we performed coculture of TGF‐β‐treated A549 cells with lung cancer cells or lung microvascular endothelial cells to evaluate the TGF‐β‐mediated invasion ability of the lung cancer cells and changes in permeability of the vascular endothelial cell layer.…”

Section: Introductionmentioning

confidence: 99%

“…Accumulating evidence revealed major transcriptional and posttranscriptional regulatory roles of long noncoding (lnc)RNAs 16 and include transcription-factor recruitment, chromatin remodeling, histone modification, pre-mRNA splicing, and as molecular sponges and scaffolds involved in the development of normal tissues or organs, as well as in carcinogenesis and the aggression of diverse malignancies. 17,18 A previous study reported that TGF-β influences microRNA (miRNA) expression in exosomes 19 ; however, the role of TGF-β in promoting exosomal lncRNA expression has not been reported. Here, we performed coculture of TGF-β-treated A549 cells with lung cancer cells or lung microvascular endothelial cells to evaluate the TGF-β-mediated invasion ability of the lung cancer cells and changes in permeability of the vascular endothelial cell layer.…”

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confidence: 99%

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TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

Deng

et al. 2018

Cancer Medicine

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Previous studies indicated that transforming growth factor (TGF)‐β‐mediated exosomal microRNAs (miRNAs) regulate the migration and invasion of lung cancer cells; however, whether and how TGF‐β‐mediated exosomal long noncoding (lnc) RNAs regulate migration and invasion of lung cancer cells remains unclear. Here, coculture experiments showed that TGF‐β pretreatment increased the migration and invasion potential of lung cancer cells and TGF‐β pretreated A549 cells increases vascular permeability. Furthermore, we found that TGF‐β‐mediated exosomes, as carriers of intercellular communication, regulated lung cancer invasion, and vascular permeability. Transcriptional analysis also revealed that lnc‐MMP2‐2 was highly enriched in TGF‐β‐mediated exosomes and might function by increasing the expression of matrix metalloproteinase (MMP)2 through its enhancer activity, with ectopic expression and silencing of lnc‐MMP2‐2 affecting lung cancer invasion and vascular permeability. Additionally, lnc‐MMP2‐2 and MMP2 expression was assessed semiquantitatively, and tissue‐specific correlations between lnc‐MMP2‐2 and MMP2 expression were evaluated. These results suggested that exosomal lnc‐MMP2‐2 might regulate the migration and invasion of lung cancer cells into the vasculature by promoting MMP2 expression, suggesting this lncRNA as a novel therapeutic target and predictive marker of tumor metastasis in lung cancer.

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

Deng

et al. 2018

Cancer Medicine

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“…Treatment with MTX alters the protein profiles of exosomes, and MTX treatment suppresses some of the changes induced by IL-1β in vitro [27]. The protein and microRNA contents of exosomes have been suggested to reflect the physiological conditions of their cells of origin; exosomes also induce phenotypic changes in their origin cells in vitro [28]. These data support the hypothesis that intracellular changes following treatment might alter exosomal contents, such as proteins and RNA.…”

Section: Discussionmentioning

confidence: 68%

Exosomal amyloid A and lymphatic vessel endothelial hyaluronic acid receptor-1 proteins are associated with disease activity in rheumatoid arthritis

et al. 2017

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BackgroundExosomes are thought to play an important role in exchanging information between cells. The proteins and lipids in exosomes play roles in mediating inflammatory and autoimmune diseases. The aim of this study was to identify exosomal candidate proteins that are related to other inflammatory parameters in rheumatoid arthritis (RA).MethodsThe study population consisted of 60 patients with RA: 30 in the clinical remission (CR) group with a Disease Activity Score in 28 joints based on erythrocyte sedimentation rate (DAS28-ESR) ≤2.6 and 30 in the non-clinical remission (non-CR) group with a DAS28-ESR >2.6. Preparation of exosomes from patient serum samples was performed with the ExoQuick kit, and protein identification/quantification was performed using tandem mass tag labeling/mass spectrometry and an enzyme-linked immunosorbent assay. Comparisons between groups were made using Student’s t test or the Mann-Whitney U test, as appropriate. Spearman’s correlation coefficients (ρ) were calculated.ResultsWe identified six candidate proteins. Exosomal levels of amyloid A (AA) and lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1) differed between the CR and non-CR groups. Both serum and exosomal AA levels were higher in the non-CR group than in the CR group (p = 0.001). Significant positive correlations were found between exosomal AA and C-reactive protein (CRP) as well as between serum AA and CRP (ρ = 0.614, p = 0.001, and ρ = 0.624, p = 0.001, respectively). Although serum levels of LYVE-1 did not differ between the non-CR and CR groups, exosomal levels of LYVE-1 were lower in the non-CR group than in the CR group (p = 0.01). We identified positive correlations between serum/exosomal LYVE-1 and CRP only in the non-CR group (serum ρ = 0.376, p = 0.04; exosome ρ = 0.545, p = 0.002).ConclusionsExosomal LYVE-1 shows potential for use as an additional marker of disease activity in patients with RA, and exosomes may carry other useful markers for RA.

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“…Exosomes, as peritoneal metastatic transplants from donor cells, promote TGF-β1-induced fibrosis by transferring TGF-β1. As the recipient cells, PMCs show increased ability to proliferate, migrate and recruit numerous fibroblasts [59]. Additionally, data from some clinical samples indicated that TGF-β1 may be overexpressed in malignant ascitesderived exosomes, and this high concentration of TGF-β1 is responsible for fibrosis [54].…”

Section: Functional Contribution Of Exosomes In Fibrosis and Angiogenmentioning

confidence: 99%

Exosomes: The New Mediator of Peritoneal Membrane Function

Shi

Sheng³

2018

Kidney Blood Press Res

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Fibrosis and angiogenesis are the most common processes that result in progressive peritoneal tissue remodeling and, eventually, peritoneal membrane dysfunction. The role of exosomes, which contributes to intercellular communication, in these processes has been neglected. Various biomolecules, including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be transferred by exosomes to local, neighboring and distal cells. Upon stimulation by cytokines or other microenvironment stimuli, donor cells release a mass of exosomes to peritoneal mesothelial cells, further affecting fibrosis and angiogenesis. This important exosomes-mediated intracellular communication is thought to regulate peritoneal membrane function. Understanding the molecular mechanisms of these processes, targeting changes in exosomes and regulating exosomal miRNAs will advance therapeutic methods for protecting peritoneal membrane function.

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Exosome cargo reflects TGF-β1-mediated epithelial-to-mesenchymal transition (EMT) status in A549 human lung adenocarcinoma cells

Cited by 104 publications

References 22 publications

TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

TGF‐β‐mediated exosomal lnc‐MMP2‐2 regulates migration and invasion of lung cancer cells to the vasculature by promoting MMP2 expression

Exosomal amyloid A and lymphatic vessel endothelial hyaluronic acid receptor-1 proteins are associated with disease activity in rheumatoid arthritis

Exosomes: The New Mediator of Peritoneal Membrane Function

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