EV-Associated MMP9 in High-Grade Serous Ovarian Cancer Is Preferentially Localized to Annexin V-Binding EVsReportar como inadecuado




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Disease Markers - Volume 2017 2017, Article ID 9653194, 9 pages - https:-doi.org-10.1155-2017-9653194

Research Article

BioSensor Technologies, AIT-Austrian Institute of Technology GmbH, Muthgasse 11, 1190 Vienna, Austria

Institute of Medical Biology, A*STAR, 8A Biomedical Grove, No. 05-05 Immunos, Singapore 138648

Molecular Oncology Group, Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Extracellular Vesicles and Membrane Repair, UMR-5248-CBMN, CNRS-University of Bordeaux-IPB, Allée Geoffroy Saint-Hilaire, 33600 Pessac, France

Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Section for Clinical Biometrics, Center for Medical Statistics, Informatics, and Intelligent Systems CeMSIIS, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Department of Surgery, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

Correspondence should be addressed to Sai Kiang Lim

Received 24 November 2016; Revised 24 January 2017; Accepted 5 April 2017; Published 18 May 2017

Academic Editor: Alvaro González

Copyright © 2017 Agnes T. Reiner et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

High-grade serous ovarian cancer HGSOC is the most aggressive type of ovarian cancer and is responsible for most deaths caused by gynecological cancers. Numerous candidate biomarkers were identified for this disease in the last decades, but most were not sensitive or specific enough for clinical applications. Hence, new biomarkers for HGSOC are urgently required. This study aimed to identify new markers by isolating different extracellular vesicle EV types from the ascites of ovarian cancer patients according to their affinities for lipid-binding proteins and analyzing their protein cargo. This approach circumvents the low signal-to-noise ratio when using biological fluids for biomarker discovery and the issue of contamination by large non-EV complexes. We isolated and analyzed three distinct EV populations from the ascites of patients with ovarian cancer or cirrhosis and observed that Annexin V-binding EVs have higher levels of matrix metalloproteinase 9 in malignant compared to portal-hypertensive ascites. As this protein was not detected in other EV populations, this study validates our approach of using different EV types for optimal biomarker discovery. Furthermore, MMP9 in Annexin V-binding EVs could be a HGSOC biomarker with enhanced specificity, because its identification requires detection of two distinct components, that is, lipid and protein.





Autor: Agnes T. Reiner, Sisareuth Tan, Christiane Agreiter, Katharina Auer, Anna Bachmayr-Heyda, Stefanie Aust, Nina Pecha, Mattia

Fuente: https://www.hindawi.com/



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