Oncotarget

Research Papers:

Modulation of paracrine signaling by CD9 positive small extracellular vesicles mediates cellular growth of androgen deprived prostate cancer

Carolina Soekmadji _, James D. Riches, Pamela J. Russell, Jayde E. Ruelcke, Stephen McPherson, Chenwei Wang, Chris M. Hovens, Niall M. Corcoran, The Australian Prostate Cancer Collaboration BioResource, Michelle M. Hill and Colleen C. Nelson

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Oncotarget. 2017; 8:52237-52255. https://doi.org/10.18632/oncotarget.11111

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Abstract

Carolina Soekmadji1,2, James D. Riches3, Pamela J. Russell1,2, Jayde E. Ruelcke2,4, Stephen McPherson1,2, Chenwei Wang1,2, Chris M. Hovens5, Niall M. Corcoran5, The Australian Prostate Cancer Collaboration BioResource6, Michelle M. Hill2,4 and Colleen C. Nelson1,2

1Australian Prostate Cancer Research Centre-Queensland, Institute of Health and Biomedical Innovation, School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia

2Translational Research Institute, Brisbane, Queensland, Australia

3Central Analytical Research Facility, Institute for Future Environments, Queensland University of Technology, Brisbane, Queensland, Australia

4The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Australia

5Australian Prostate Cancer Research Centre Epworth, and Department of Surgery, University of Melbourne, Australia

6Australian Prostate Cancer Collaboration (APCC) Bioresource, Brisbane, Queensland, Australia

Correspondence to:

Carolina Soekmadji, email: soekmadji@yahoo.com

Keywords: prostate cancer, androgen receptor, extracellular vesicles, CD9, exosomes

Received: October 03, 2015    Accepted: July 16, 2016    Published: August 08, 2016

ABSTRACT

Proliferation and maintenance of both normal and prostate cancer (PCa) cells is highly regulated by steroid hormones, particularly androgens, and the extracellular environment. Herein, we identify the secretion of CD9 positive extracellular vesicles (EV) by LNCaP and DUCaP PCa cells in response to dihydrotestosterone (DHT) and use nano-LC–MS/MS to identify the proteins present in these EV. Subsequent bioinformatic and pathway analyses of the mass spectrometry data identified pathologically relevant pathways that may be altered by EV contents. Western blot and CD9 EV TR-FIA assay confirmed a specific increase in the amount of CD9 positive EV in DHT-treated LNCaP and DUCaP cells and treatment of cells with EV enriched with CD9 after DHT exposure can induce proliferation in androgen-deprived conditions. siRNA knockdown of endogenous CD9 in LNCaPs reduced cellular proliferation and expression of AR and prostate specific antigen (PSA) however knockdown of AR did not alter CD9 expression, also implicating CD9 as an upstream regulator of AR. Moreover CD9 positive EV were also found to be significantly higher in plasma from prostate cancer patients in comparison with benign prostatic hyperplasia patients. We conclude that CD9 positive EV are involved in mediating paracrine signalling and contributing toward prostate cancer progression.


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