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      Extracellular vesicles, tissue factor, cancer and thrombosis – discussion themes of the ISEV 2014 Educational Day

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          Abstract

          Although the association between cancer and venous thromboembolism (VTE) has long been known, the mechanisms are poorly understood. Circulating tissue factor–bearing extracellular vesicles have been proposed as a possible explanation for the increased risk of VTE observed in some types of cancer. The International Society for Extracellular Vesicles (ISEV) and International Society on Thrombosis and Haemostasis (ISTH) held a joint Educational Day in April 2014 to discuss the latest developments in this field. This review discusses the themes of that event and the ISEV 2014 meeting that followed.

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          Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer.

          Christoph Kahlert, Sonia A. Melo, Alexei Protopopov … (2014)
          Exosomes are small vesicles (50-150 nm) of endocytic origin that are released by many different cell types. Exosomes in the tumor microenvironment may play a key role in facilitating cell-cell communication. Exosomes are reported to predominantly contain RNA and proteins. In this study, we investigated whether exosomes from pancreatic cancer cells and serum from patients with pancreatic ductal adenocarcinoma contain genomic DNA. Our results provide evidence that exosomes contain >10-kb fragments of double-stranded genomic DNA. Mutations in KRAS and p53 can be detected using genomic DNA from exosomes derived from pancreatic cancer cell lines and serum from patients with pancreatic cancer. In addition, using whole genome sequencing, we demonstrate that serum exosomes from patients with pancreatic cancer contain genomic DNA spanning all chromosomes. These results indicate that serum-derived exosomes can be used to determine genomic DNA mutations for cancer prediction, treatment, and therapy resistance.
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            Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

            Mario L Suvà, Esther Rheinbay, Shawn M Gillespie … (2014)
            Developmental fate decisions are dictated by master transcription factors (TFs) that interact with cis-regulatory elements to direct transcriptional programs. Certain malignant tumors may also depend on cellular hierarchies reminiscent of normal development but superimposed on underlying genetic aberrations. In glioblastoma (GBM), a subset of stem-like tumor-propagating cells (TPCs) appears to drive tumor progression and underlie therapeutic resistance yet remain poorly understood. Here, we identify a core set of neurodevelopmental TFs (POU3F2, SOX2, SALL2, and OLIG2) essential for GBM propagation. These TFs coordinately bind and activate TPC-specific regulatory elements and are sufficient to fully reprogram differentiated GBM cells to "induced" TPCs, recapitulating the epigenetic landscape and phenotype of native TPCs. We reconstruct a network model that highlights critical interactions and identifies candidate therapeutic targets for eliminating TPCs. Our study establishes the epigenetic basis of a developmental hierarchy in GBM, provides detailed insight into underlying gene regulatory programs, and suggests attendant therapeutic strategies. PAPERCLIP: Copyright © 2014 Elsevier Inc. All rights reserved.
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              Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy.

              Huilin Shao, Jaehoon Chung, Leonora Balaj … (2012)
              Glioblastomas shed large quantities of small, membrane-bound microvesicles into the circulation. Although these hold promise as potential biomarkers of therapeutic response, their identification and quantification remain challenging. Here, we describe a highly sensitive and rapid analytical technique for profiling circulating microvesicles directly from blood samples of patients with glioblastoma. Microvesicles, introduced onto a dedicated microfluidic chip, are labeled with target-specific magnetic nanoparticles and detected by a miniaturized nuclear magnetic resonance system. Compared with current methods, this integrated system has a much higher detection sensitivity and can differentiate glioblastoma multiforme (GBM) microvesicles from nontumor host cell-derived microvesicles. We also show that circulating GBM microvesicles can be used to analyze primary tumor mutations and as a predictive metric of treatment-induced changes. This platform could provide both an early indicator of drug efficacy and a potential molecular stratifier for human clinical trials.
              Article 0 comments Cited 268 times – based on 0 reviews     Review now
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Extracell Vesicles
                Journal ID (iso-abbrev): J Extracell Vesicles
                Journal ID (publisher-id): JEV
                Title: Journal of Extracellular Vesicles
                Publisher: Co-Action Publishing
                ISSN (Electronic): 2001-3078
                Publication date (Electronic): 13 March 2015
                Publication date Collection: 2015
                Volume: 4
                Electronic Location Identifier: 10.3402/jev.v4.26901
                Affiliations
                [1 ]Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3 Women's Centre, John Radcliffe Hospital, Oxford, UK
                [2 ]School of Immunity and Infection, University of Birmingham Medical School, Birmingham, UK
                [3 ]Department of Oncology and Pathology, Clinical Sciences, Skåne University Hospital, Lund, Sweden
                [4 ]Department of Clinical Chemistry, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands
                [5 ]Department of Cardiologic, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy
                [6 ]Division of Neurosurgery, University of California San Diego, La Jolla, CA, USA
                [7 ]Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, UK
                [8 ]Department of Biomedical Engineering and Physics, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands
                [9 ]School of Biological, Biomedical and Environmental Sciences, The University of Hull, Hull, UK
                [10 ]Department of Vascular Medicine, Academic Medical Centre of the University of Amsterdam, Amsterdam, The Netherlands
                [11 ]Department of Neurology and Program in Neuroscience, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
                [12 ]Thrombosis and Hemostasis Program, Department of Medicine, UNC McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
                [13 ]Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
                [14 ]Department of Pediatrics, McGill University, Montreal Children's Hospital Research Institute MUHC, Montreal, QC, Canada
                Author notes
                [* ]Correspondence to: Chris Gardiner, Nuffield Department of Obstetrics and Gynaecology, University of Oxford, Level 3, Women’s Centre, John Radcliffe Hospital, Oxford, OX3 9DU, UK, Email: chris.gardiner@ 123456obs-gyn.ox.ac.uk
                Article
                Publisher ID: 26901
                DOI: 10.3402/jev.v4.26901
                PMC ID: 4359985
                PubMed ID: 25773446
                SO-VID: 749d3386-a54a-4f90-939b-69c29d6fdcef
                Copyright © © 2015 Chris Gardiner et al.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 07 December 2014
                Date revision received : 11 February 2015
                Date accepted : 18 February 2015
                Categories
                Subject: Review Article

                Keywords: extracellular vesicles,thrombosis,cancer,tissue factor
                Data availability:
                Keywords: extracellular vesicles, thrombosis, cancer, tissue factor

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