INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Biomedical Research and Innovation Institute (IRIB), University of Rouen, Mont-Saint-Aignan, France.
University Paris-Diderot, Sorbonne Paris Cité, CRB3, Centre de Recherche Biomédicale Bichat Beaujon (CRB3), UMR773, INSERM, F-75018 Paris, France.
Eur J Cancer. 2014 Aug;50(12):2126-33. doi: 10.1016/j.ejca.2014.05.008. Epub 2014 Jun 5.
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.
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.
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 AI 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.
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.
本研究旨在探讨食欲素及其受体在前列腺癌（CaP）中的存在，并研究其对前列腺癌细胞凋亡的影响。
我们对不同分级的 CaP 组织中食欲素 1 型和 2 型受体（OX1R 和 OX2R）及食欲素 A（OxA）进行了定位，并对含有 OX1R 的肿瘤细胞进行了定量。我们在雄激素依赖性（AD）LNCaP 和雄激素非依赖性（AI）DU145 前列腺癌细胞中评估了 OX1R 的表达，这些细胞是否经历了神经内分泌分化。我们还研究了食欲素对 DU145 细胞凋亡和活力的影响。
OX1R 在表现出神经内分泌分化的癌灶中强烈表达，并且具有 OX1R 染色的癌细胞数量随着 CaP 的分级增加而增加。相比之下，OX2R 仅在高级别 CaP 中的散在恶性细胞中检测到。OX1R 在 AI DU145 细胞中表达，但在 LNCaP 细胞中检测不到。DU145 细胞获得神经内分泌表型与 OX1R 的过度表达相关。食欲素诱导经历神经内分泌分化的 DU145 细胞凋亡。
本研究数据表明，在表现出神经内分泌分化的 AI CaP 中，OX1R 驱动的凋亡过度表达，为这些目前尚无治愈方法的侵袭性癌症开辟了新的治疗途径。
