The orexin type 1 receptor is overexpressed in advanced prostate cancer with a neuroendocrine differentiation, and mediates apoptosis

被引：39
作者：
Alexandre, David [1 ]
Hautot, Coralie [1 ]
Mehio, Marwa [1 ]
Jeandel, Lydie [1 ]
Courel, Maite [1 ]
Voisin, Thierry [2 ]
Couvineau, Alain [2 ]
Gobet, Francoise [3 ]
Leprince, Jerome [1 ]
Pfister, Christian [4 ]
Anouar, Youssef [1 ]
Chartrel, Nicolas [1 ]
机构：
[1] Univ Rouen, Biomed Res & Innovat Inst IRIB, Lab Neuronal & Neuroendocrine Differentiat & Comm, INSERM U982, F-76821 Mont St Aignan, France
[2] Univ Paris Diderot, Sorbonne Paris Cite, CRB3, UMR773,INSERM, F-75018 Paris, France
[3] Univ Rouen, Inst Biomed Res, Univ Hosp Rouen, Dept Pathol, Rouen, France
[4] Univ Rouen, Inst Biomed Res, Univ Hosp Rouen, Dept Urol, Rouen, France
来源：
EUROPEAN JOURNAL OF CANCER | 2014年 / 50卷 / 12期
关键词：
Neuropeptide; G protein-coupled receptor; Neuroendocrine differentiation; Cancer; Apoptosis; Proliferation; Prostate cancer therapy; COLON-CANCER; CELLS; EXPRESSION; MIGRATION; PEPTIDE; ADRENOMEDULLIN; PROLIFERATION; VIP;
D O I：
10.1016/j.ejca.2014.05.008
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
Aim: In the present study, we have examined the presence of orexins and their receptors in prostate cancer (CaP) and investigated their effects on the apoptosis of prostate cancer cells. Methods: We have localised the orexin type 1 and 2 receptors (OX1R and OX2R) and orexin A (OxA) in CaP sections of various grades and we have quantified tumour cells containing OX1R. Expression of OX1R was evaluated in the androgeno-dependent (AD) LNCaP and the androgeno-independent (AI) DU145 prostate cancer cells submitted or not to a neuroendocrine differentiation. The effects of orexins on the apoptosis and viability of DU145 cells were also investigated. Results: OX1R is strongly expressed in carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of OX1R-stained cancer cells increases with the grade of the CaP. In contrast, OX2R is only detected in scattered malignant cells in high grade CaP. OX1R is expressed in the AT DU145 cells but is undetectable in the LNCaP cells. Acquisition of a neuroendocrine phenotype by the DU145 cells is associated with an overexpression of OX1R. Orexins induce the apoptosis of DU145 cells submitted to a neuroendocrine differentiation. Conclusion: The present data indicate that OX1R-driven apoptosis is overexpressed in AI CaP exhibiting a neuroendocrine differentiation opening a gate for novel therapies for these aggressive cancers which are incurable until now. (C) 2014 Elsevier Ltd. All rights reserved.
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页码：2126 / 2133
页数：8
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