Cross-talk between alpha1D-adrenoceptors and transient receptor potential vanilloid type 1 triggers prostate cancer cell proliferation

BMC Cancer

Maria Beatrice Morelli²  Consuelo Amantini⁴  Massimo Nabissi²  Sonia Liberati⁵  Claudio Cardinali⁵  Valerio Farfariello¹  Daniele Tomassoni⁴  Wilma Quaglia⁶  Alessandro Piergentili⁶  Alessandro Bonifazi⁶  Fabio Del Bello⁶  Matteo Santoni⁸  Gabriele Mammana³  Lucilla Servi³  Alessandra Filosa⁷  Angela Gismondi⁵  Giorgio Santoni² 

[1] Istituto Pasteur - Fondazione Cenci-Bolognetti, Rome 00161, Italy

[2] School of Pharmacy, Section of Experimental Medicine, University of Camerino, Camerino 62032, Italy

[3] Urology Unit, ASUR 9, Macerata 62100, Italy

[4] School of Biosciences and Veterinary Medicine, University of Camerino, Camerino 62032, Italy

[5] Department of Molecular Medicine, Sapienza University, Rome 00161, Italy

[6] School of Pharmacy, Medicinal Chemistry Unit, University of Camerino, Camerino 62032, Italy

[7] Pathology Unit, ASUR 9, Macerata 62100, Italy

[8] Department of Medical Oncology, AOU Ospedali Riuniti, Polytechnic University of Marche, Ancona 60126, Italy

关键词: Prostate cancer;    PC3 cell line;    Proliferation;    Noradrenaline;    Transient receptor potential vanilloid type 1;    α_1D-adrenoceptors;   

Others  :  1117936
DOI  :  10.1186/1471-2407-14-921

 received in 2014-04-29, accepted in 2014-11-25,  发布年份 2014

【 摘 要 】

Background

There is evidence that calcium (Ca²⁺) 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, Ca²⁺ flux, IP₃ 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 Ca²⁺ 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.

【 授权许可】

   
2014 Morelli et al.; licensee BioMed Central Ltd.

【 图 表 】

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