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Androgens alter the heterogeneity of small extracellular vesicles and the small RNA cargo in prostate cancer.

Authors :
Martens-Uzunova ES
Kusuma GD
Crucitta S
Lim HK
Cooper C
Riches JE
Azad A
Ochiya T
Boyle GM
Southey MC
Del Re M
Lim R
Ramm GA
Jenster GW
Soekmadji C
Source :
Journal of extracellular vesicles [J Extracell Vesicles] 2021 Aug; Vol. 10 (10), pp. e12136. Date of Electronic Publication: 2021 Aug 18.
Publication Year :
2021

Abstract

Proliferation and survival of prostate cancer cells are driven by the androgen receptor (AR) upon binding to androgen steroid hormones. Manipulating the AR signalling axis is the focus for prostate cancer therapy; thus, it is crucial to understand the role of androgens and AR on extracellular vesicle (EV) secretion and cargo. In this study, we report that plasma-derived circulating vesicles consisting of CD9 and double-positive for CD9 and Prostate Specific Membrane Antigen (PSMA) are increased in patients with advanced metastatic prostate cancer, whereas double positives for CD9 and CD63 small extracellular vesicles (S-EVs) are significantly higher in patients with localised prostate cancer. Androgen manipulation by dihydrotestosterone (DHT) and the clinical antagonist enzalutamide (ENZ) altered the heterogeneity and size of CD9 positive S-EVs in AR expressing prostate cancer cells, while assessment of the total number and protein cargo of total S-EVs was unaltered across different treatment groups. Furthermore, hormone stimulation caused strong and specific effects on the small RNA cargo of S-EVs. A total of 543 small RNAs were found to be regulated by androgens including miR-19-3p and miR-361-5p. Analysis of S-EVs heterogeneity and small RNA cargo may provide clinical utility for prostate cancer and be informative to understand further the mechanism of resistance to androgen targeted therapy in castration-resistant prostate cancer.<br />Competing Interests: The authors have declared no conflict of interest.<br /> (© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.)

Details

Language :
English
ISSN :
2001-3078
Volume :
10
Issue :
10
Database :
MEDLINE
Journal :
Journal of extracellular vesicles
Publication Type :
Academic Journal
Accession number :
34434533
Full Text :
https://doi.org/10.1002/jev2.12136