University of Oulu

Bert Dhondt, Edward Geeurickx, Joeri Tulkens, Jan Van Deun, Glenn Vergauwen, Lien Lippens, Ilkka Miinalainen, Pekka Rappu, Jyrki Heino, Piet Ost, Nicolaas Lumen, Olivier De Wever & An Hendrix (2020) Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine, Journal of Extracellular Vesicles, 9:1, DOI: 10.1080/20013078.2020.1736935

Unravelling the proteomic landscape of extracellular vesicles in prostate cancer by density-based fractionation of urine

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Author: Dhondt, Bert1,2,3; Geeurickx, Edward1,2; Tulkens, Joeri1,2;
Organizations: 1Laboratory of Experimental Cancer Research, Department of Human Structure and Repair, Ghent University, Ghent, Belgium
2Cancer Research Institute Ghent, Ghent, Belgium
3Department of Urology, Ghent University Hospital, Ghent, Belgium
4Department of Gynaecology, Ghent University Hospital, Ghent, Belgium
5Biocenter Oulu, Department of Pathology, Oulu University Hospital, University of Oulu, Oulu, Finland
6Department of Biochemistry, University of Turku, Turku, Finland
7Department of Radiation Oncology, Ghent University Hospital, Ghent, Belgium
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.5 MB)
Persistent link: http://urn.fi/urn:nbn:fi-fe2020062245268
Language: English
Published: Informa, 2020
Publish Date: 2020-06-22
Description:

Abstract

Extracellular vesicles (EV) are increasingly being recognized as important vehicles of intercellular communication and promising diagnostic and prognostic biomarkers in cancer. Despite this enormous clinical potential, the plethora of methods to separate EV from biofluids, providing material of highly variable purity, and lacking knowledge regarding methodological repeatability pose a barrier to clinical translation. Urine is considered an ideal proximal fluid for the study of EV in urological cancers due to its direct contact with the urogenital system. We demonstrate that density-based fractionation of urine by bottom-up Optiprep density gradient centrifugation separates EV and soluble proteins with high specificity and repeatability. Mass spectrometry-based proteomic analysis of urinary EV (uEV) in men with benign and malignant prostate disease allowed us to significantly expand the known human uEV proteome with high specificity and identifies a unique biological profile in prostate cancer not uncovered by the analysis of soluble proteins. In addition, profiling the proteome of EV separated from prostate tumour conditioned medium and matched uEV confirms the specificity of the identified uEV proteome for prostate cancer. Finally, a comparative proteomic analysis with uEV from patients with bladder and renal cancer provided additional evidence of the selective enrichment of protein signatures in uEV reflecting their respective cancer tissues of origin. In conclusion, this study identifies hundreds of previously undetected proteins in uEV of prostate cancer patients and provides a powerful toolbox to map uEV content and contaminants ultimately allowing biomarker discovery in urological cancers.

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Series: Journal of extracellular vesicles
ISSN: 2001-3078
ISSN-E: 2001-3078
ISSN-L: 2001-3078
Volume: 9
Issue: 1
Article number: 1736935
DOI: 10.1080/20013078.2020.1736935
OADOI: https://oadoi.org/10.1080/20013078.2020.1736935
Type of Publication: A1 Journal article – refereed
Field of Science: 3122 Cancers
3111 Biomedicine
Subjects:
Funding: This work was supported by the Fund for Scientific Spearheads of Ghent University Hospital, Concerted Research Actions from Ghent University, “Stichting tegen Kanker”, the Fund for Scientific Research-Flanders and “Kom op tegen Kanker (Stand up to Cancer), the Flemisch cancer society”.
Copyright information: © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
  https://creativecommons.org/licenses/by-nc/4.0/