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Open AccessArticle

Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer

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Translational Genomics Group and Targeted Therapeutics in Solid Tumors, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
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Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain
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Medical Oncology Department, Hospital Clínic, 08036 Barcelona, Spain
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Department of Human Oncology, University of Wisconsin-Madison, Madison, WI 53706, USA
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Genomic Unit, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain
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Department and Laboratory of Urology, Hospital Clínic, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centre de Recerca Biomèdica CELLEX, 08036 Barcelona, Spain
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Department of Biomedicine, University of Barcelona, 08007 Barcelona, Spain
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Immunology Department, Hospital Clínic, 08036 Barcelona, Spain
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Department of Medicine, University of Barcelona, 08036 Barcelona, Spain
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Author to whom correspondence should be addressed.
Cells 2020, 9(1), 203; https://doi.org/10.3390/cells9010203 (registering DOI)
Received: 10 December 2019 / Revised: 9 January 2020 / Accepted: 10 January 2020 / Published: 14 January 2020
Androgen receptor (AR) signaling remains crucial in castration-resistant prostate cancer (CRPC). Since it is also essential in immune cells, we studied whether the expression of AR full-length (ARFL) and its splicing variant ARV7 in peripheral blood mononuclear cells (PBMC) predicts systemic treatment response in mCRPC in comparison with circulating-tumor cells (CTC). We measured ARFL and ARV7 mRNA in PBMC and CTC from patients prior to receiving abiraterone (AA), enzalutamide (E), or taxanes by a pre-amplification plus quantitative reverse-transcription PCR. They were also tested in LNCaP-ARV7-transfected and in 22RV1 docetaxel-resistant (22RV1DR) cells. We studied 171 PBMC from 136 patients and from 24 non-cancer controls, and 47 CTC from 22 patients. High PBMC ARV7 levels correlated with worse AA/E and better taxane response. In taxane-treated patients high PBMC ARFL also correlated with longer progression-free survival (PFS). High ARV7 and ARFL expression were independently associated with better biochemical-PFS. Conversely, high CTC ARV7 and ARFL correlated with shorter radiological-PFS and overall survival, respectively. High ARV7 in 22RV1DR and LNCaP-ARV7 cells correlated with taxane resistance. In conclusion, ARFL and ARV7 at PBMC or CTC have a different predictive role in the taxane response, suggesting a potential influence of the AR pathway from PBMC in such response modulation. View Full-Text
Keywords: abiraterone; androgen receptor; androgen receptor splicing variant 7; castration-resistant prostate cancer; enzalutamide; peripheral blood mononuclear cells; taxanes abiraterone; androgen receptor; androgen receptor splicing variant 7; castration-resistant prostate cancer; enzalutamide; peripheral blood mononuclear cells; taxanes
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Marín-Aguilera, M.; Jiménez, N.; Reig, Ò.; Montalbo, R.; Verma, A.K.; Castellano, G.; Mengual, L.; Victoria, I.; Pereira, M.V.; Milà-Guasch, M.; García-Recio, S.; Benítez-Ribas, D.; Cabezón, R.; González, A.; Juan, M.; Prat, A.; Mellado, B. Androgen Receptor and Its Splicing Variant 7 Expression in Peripheral Blood Mononuclear Cells and in Circulating Tumor Cells in Metastatic Castration-Resistant Prostate Cancer. Cells 2020, 9, 203.

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