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

Autor: Elena S. Martens‐Uzunova, Gina D. Kusuma, Stefania Crucitta, Hong Kiat Lim, Crystal Cooper, James E. Riches, Arun Azad, Takahiro Ochiya, Glen M. Boyle, Melissa C. Southey, Marzia Del Re, Rebecca Lim, Grant A. Ramm, Guido W. Jenster, Carolina Soekmadji
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Journal of Extracellular Vesicles, Vol 10, Iss 10, Pp n/a-n/a (2021)
Druh dokumentu: article
ISSN: 2001-3078
DOI: 10.1002/jev2.12136
Popis: 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.
Databáze: Directory of Open Access Journals
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