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Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation

BACKGROUND: There is evidence that calcium (Ca(2+)) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha(1D)-adrenergic receptor (alpha(1D)-AR) and the transient receptor...

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Autores principales: Morelli, Maria Beatrice, Amantini, Consuelo, Nabissi, Massimo, Liberati, Sonia, Cardinali, Claudio, Farfariello, Valerio, Tomassoni, Daniele, Quaglia, Wilma, Piergentili, Alessandro, Bonifazi, Alessandro, Del Bello, Fabio, Santoni, Matteo, Mammana, Gabriele, Servi, Lucilla, Filosa, Alessandra, Gismondi, Angela, Santoni, Giorgio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306515/
https://www.ncbi.nlm.nih.gov/pubmed/25481381
http://dx.doi.org/10.1186/1471-2407-14-921
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author Morelli, Maria Beatrice
Amantini, Consuelo
Nabissi, Massimo
Liberati, Sonia
Cardinali, Claudio
Farfariello, Valerio
Tomassoni, Daniele
Quaglia, Wilma
Piergentili, Alessandro
Bonifazi, Alessandro
Del Bello, Fabio
Santoni, Matteo
Mammana, Gabriele
Servi, Lucilla
Filosa, Alessandra
Gismondi, Angela
Santoni, Giorgio
author_facet Morelli, Maria Beatrice
Amantini, Consuelo
Nabissi, Massimo
Liberati, Sonia
Cardinali, Claudio
Farfariello, Valerio
Tomassoni, Daniele
Quaglia, Wilma
Piergentili, Alessandro
Bonifazi, Alessandro
Del Bello, Fabio
Santoni, Matteo
Mammana, Gabriele
Servi, Lucilla
Filosa, Alessandra
Gismondi, Angela
Santoni, Giorgio
author_sort Morelli, Maria Beatrice
collection PubMed
description BACKGROUND: There is evidence that calcium (Ca(2+)) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha(1D)-adrenergic receptor (alpha(1D)-AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha(1D)-AR to cross-talk with TRPV1 in PCa cell lines. METHODS: The expression of alpha(1D)-AR and TRPV1 was examined in human PCa tissues by quantitative RT-PCR and in PCa cell lines (DU145, PC3 and LNCaP) by cytofluorimetry. Moreover, alpha(1D)-AR and TRPV1 colocalization was investigated by confocal microscopy in PCa cell lines and by fluorescence microscopy in benign prostate hyperplasia (BPH) and PCa tissues. Cell proliferation was assessed by BrdU incorporation. Alpha(1D)-AR/TRPV1 knockdown was obtained using siRNA transfection. Signalling pathways were evaluated by measurement of extracellular acidification rate, Ca(2+) flux, IP(3) production, western blot and MTT assay. RESULTS: The levels of the alpha(1D)-AR and TRPV1 mRNAs are increased in PCa compared to BPH specimens and a high correlation between alpha(1D)-AR and TRPV1 expression levels was found. Moreover, alpha(1D)-AR and TRPV1 are co-expressed in prostate cancer cell lines and specimens. Noradrenaline (NA) induced an alpha(1D)-AR- and TRPV1-dependent protons release and Ca(2+) flux in PC3 cell lines; NA by triggering the activation of phospholipase C (PLC), protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways stimulated PC3 cell proliferation, that was completely inhibited by clopenphendioxan (WS433) and capsazepine (CPZ) combination or by alpha(1D)-AR/TRPV1 double knockdown. CONCLUSIONS: We demonstrate a cross-talk between alpha(1D)-AR and TRPV1, that is involved in the control of PC3 cell proliferation. These data strongly support for a putative novel pharmacological approach in the treatment of PCa by targeting both alpha(1D)-AR and TRPV1 channels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-921) contains supplementary material, which is available to authorized users.
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spelling pubmed-43065152015-01-27 Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation Morelli, Maria Beatrice Amantini, Consuelo Nabissi, Massimo Liberati, Sonia Cardinali, Claudio Farfariello, Valerio Tomassoni, Daniele Quaglia, Wilma Piergentili, Alessandro Bonifazi, Alessandro Del Bello, Fabio Santoni, Matteo Mammana, Gabriele Servi, Lucilla Filosa, Alessandra Gismondi, Angela Santoni, Giorgio BMC Cancer Research Article BACKGROUND: There is evidence that calcium (Ca(2+)) increases the proliferation of human advanced prostate cancer (PCa) cells but the ion channels involved are not fully understood. Here, we investigated the correlation between alpha(1D)-adrenergic receptor (alpha(1D)-AR) and the transient receptor potential vanilloid type 1 (TRPV1) expression levels in human PCa tissues and evaluated the ability of alpha(1D)-AR to cross-talk with TRPV1 in PCa cell lines. METHODS: The expression of alpha(1D)-AR and TRPV1 was examined in human PCa tissues by quantitative RT-PCR and in PCa cell lines (DU145, PC3 and LNCaP) by cytofluorimetry. Moreover, alpha(1D)-AR and TRPV1 colocalization was investigated by confocal microscopy in PCa cell lines and by fluorescence microscopy in benign prostate hyperplasia (BPH) and PCa tissues. Cell proliferation was assessed by BrdU incorporation. Alpha(1D)-AR/TRPV1 knockdown was obtained using siRNA transfection. Signalling pathways were evaluated by measurement of extracellular acidification rate, Ca(2+) flux, IP(3) production, western blot and MTT assay. RESULTS: The levels of the alpha(1D)-AR and TRPV1 mRNAs are increased in PCa compared to BPH specimens and a high correlation between alpha(1D)-AR and TRPV1 expression levels was found. Moreover, alpha(1D)-AR and TRPV1 are co-expressed in prostate cancer cell lines and specimens. Noradrenaline (NA) induced an alpha(1D)-AR- and TRPV1-dependent protons release and Ca(2+) flux in PC3 cell lines; NA by triggering the activation of phospholipase C (PLC), protein kinase C (PKC) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways stimulated PC3 cell proliferation, that was completely inhibited by clopenphendioxan (WS433) and capsazepine (CPZ) combination or by alpha(1D)-AR/TRPV1 double knockdown. CONCLUSIONS: We demonstrate a cross-talk between alpha(1D)-AR and TRPV1, that is involved in the control of PC3 cell proliferation. These data strongly support for a putative novel pharmacological approach in the treatment of PCa by targeting both alpha(1D)-AR and TRPV1 channels. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1471-2407-14-921) contains supplementary material, which is available to authorized users. BioMed Central 2014-12-07 /pmc/articles/PMC4306515/ /pubmed/25481381 http://dx.doi.org/10.1186/1471-2407-14-921 Text en © Morelli et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Morelli, Maria Beatrice
Amantini, Consuelo
Nabissi, Massimo
Liberati, Sonia
Cardinali, Claudio
Farfariello, Valerio
Tomassoni, Daniele
Quaglia, Wilma
Piergentili, Alessandro
Bonifazi, Alessandro
Del Bello, Fabio
Santoni, Matteo
Mammana, Gabriele
Servi, Lucilla
Filosa, Alessandra
Gismondi, Angela
Santoni, Giorgio
Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title_full Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title_fullStr Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title_full_unstemmed Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title_short Cross-talk between alpha(1D)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
title_sort cross-talk between alpha(1d)-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306515/
https://www.ncbi.nlm.nih.gov/pubmed/25481381
http://dx.doi.org/10.1186/1471-2407-14-921
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