Exosome-Mediated Metastasis: From Epithelial–Mesenchymal Transition to Escape from Immunosurveillance

Syn, Nicholas; Wang, Lingzhi; Sethi, Gautam; Thiery, Jean Paul; Goh, Boon Cher

doi:10.1016/j.tips.2016.04.006

Cited by 422 publications

(334 citation statements)

References 76 publications

Supporting

Mentioning

331

Contrasting

Order By: Relevance

“…It was reported that tumor-derived exosomes could enhance metastasis by bone marrow education [34], and that exosomes may participate in tumor metastasis via exosomal miRNAs [35, 36]. Exosomes also play important roles in stromal remodelling and immune regulation in cancer [37, 38]. …”

Section: Discussionmentioning

confidence: 99%

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer

et al. 2016

View full text Add to dashboard Cite

Exosomal miRNAs are proposed as excellent candidate biomarkers for clinical applications. However, little is known about their potential roles as prognostic biomarkers in lung cancer. In this study, we explored the prognostic value of plasma exosomal microRNAs (miRNAs) for non-small-cell lung cancer (NSCLC). Using a quantitative polymerase chain reaction (qPCR) array panel, we analyzed 84 plasma exosomal miRNAs in 10 lung adenocarcinoma patients and 10 matched healthy controls. The qPCR array showed 30 aberrantly expressed exosomal miRNAs. Nine candidate miRNAs were selected based on differential expression and previous reports for further evaluating their prognostic roles in 196 NSCLC patients. Elevated levels of exosomal miR-23b-3p, miR-10b-5p and miR-21-5p were independently associated with poor overall survival (with hazard ratio [95% confidence interval]: 2.42 (1.45 - 4.04), P = 0.001; 2.22 (1.18 - 4.16), P = 0.013; 2.12 (1.28 - 3.49), P = 0.003, respectively). When compared to the clinical prognostic variables only model, adding the three exosomal miRNA signatures significantly improved survival predictive accuracy with an increase of time-dependent area under the receiver operating characteristic curve from 0.88 to 0.91 (P=0.015). Our results indicated that plasma exosomal miR-23b-3p, miR-10b-5p and miR-21-5p are promising non-invasive prognostic biomarkers of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Interestingly, CD73 is expressed not only on MSC but also on tumor cells and Treg cells, suggesting that the adenosine found within TME can be derived from different sources, to further amplify the strong inhibitory effect derived from a single cell type [13,14,15]. Transglutaminase (TG)-II can be used to selectively identify MSC in immunohistochemistry and cytofluorimetry [16,17,18,19,20,21,22,23]; however, it is also expressed on tumor cells undergoing EMT. TG-II is involved in several processes that can regulate tumor cell proliferation and apoptosis [16,17,18,19,20,21].…”

Section: Msc Phenotypic and Functional Features Relevant In The Inmentioning

confidence: 99%

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Poggi

Giuliani

2016

Vaccines

View full text Add to dashboard Cite

The tumor microenvironment is a good target for therapy in solid tumors and hematological malignancies. Indeed, solid tumor cells’ growth and expansion can influence neighboring cells’ behavior, leading to a modulation of mesenchymal stromal cell (MSC) activities and remodeling of extracellular matrix components. This leads to an altered microenvironment, where reparative mechanisms, in the presence of sub-acute inflammation, are not able to reconstitute healthy tissue. Carcinoma cells can undergo epithelial mesenchymal transition (EMT), a key step to generate metastasis; these mesenchymal-like cells display the functional behavior of MSC. Furthermore, MSC can support the survival and growth of leukemic cells within bone marrow participating in the leukemic cell niche. Notably, MSC can inhibit the anti-tumor immune response through either carcinoma-associated fibroblasts or bone marrow stromal cells. Experimental data have indicated their relevance in regulating cytolytic effector lymphocytes of the innate and adaptive arms of the immune system. Herein, we will discuss some of the evidence in hematological malignancies and solid tumors. In particular, we will focus our attention on the means by which it is conceivable to inhibit MSC-mediated immune suppression and trigger anti-tumor innate immunity.

show abstract

“…In NK cells, down-regulation in expression of the activating receptors, especially NKG2D, is induced by TEX carrying MICA and MICB ligands [41]. NK-cell activation and cytotoxicity is inhibited by TGF-β, which is prominently displayed on TEX as transforming growth factor-latency associated protein (TGF-LAP) (Figure 2), the form necessary for TGF-β activation upon binding to integrins, e.g., α6βV, on the surface of recipient cells [42]. TEX, which are able to make adenosine from ATP by virtue of carrying CD39 and CD73 [38] are implicated in inducing suppressive activity in activated B cells, because adenosine can convert activated B cells into regulatory B cells [43].…”

Section: Mechanism Of Tex-mediated Suppression In Other Immune Cellsmentioning

confidence: 99%

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

Whiteside

2016

Vaccines

View full text Add to dashboard Cite

Tumor-derived exosomes (TEX) are emerging as critical components of an intercellular information network between the tumor and the host. The tumor escapes from the host immune system by using a variety of mechanisms designed to impair or eliminate anti-tumor immunity. TEX carrying a cargo of immunoinhibitory molecules and factors represent one such mechanism. TEX, which are present in all body fluids of cancer patients, deliver negative molecular or genetic signals to immune cells re-programming their functions. Although TEX can also stimulate immune activity, in the microenvironments dominated by the tumor, TEX tend to mediate immune suppression thus promoting tumor progression. The TEX content, in part resembling that of the parent cell, may serve as a source of cancer biomarkers. TEX also interfere with immune therapies. A better understanding of TEX and their contribution to cancer progression and cancer patients’ response to immune therapies represents a challenging new field of investigation.

show abstract

Exosome-Mediated Metastasis: From Epithelial–Mesenchymal Transition to Escape from Immunosurveillance

Cited by 422 publications

References 76 publications

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer

Circulating exosomal microRNAs as prognostic biomarkers for non-small-cell lung cancer

Mesenchymal Stromal Cells Can Regulate the Immune Response in the Tumor Microenvironment

Tumor-Derived Exosomes and Their Role in Tumor-Induced Immune Suppression

Contact Info

Product

Resources

About