University of Rouen, Mont-Saint-Aignan, France.
Eur J Cancer. 2013 Jan;49(2):511-9. doi: 10.1016/j.ejca.2012.05.028. Epub 2012 Aug 3.
Accumulating data suggest that neuropeptides produced by neuroendocrine cells play a crucial role in the progression and aggressiveness of hormone refractory prostate cancer (CaP). In this study, we have investigated the presence and function of the neuropeptide 26RFa in CaP.
We have localised and quantified tumour cells containing 26RFa and its receptor, GPR103, in CaP sections of various grades. In vitro experiments were performed to investigate the effects of 26RFa on the migration, proliferation and neuroendocrine differentiation of the androgeno-independent (AI) prostate cancer cell line DU145.
26RFa and GPR103 are present in carcinomatous foci exhibiting a neuroendocrine differentiation, and the number of 26RFa and GPR103-immunoreactive cancer cells increases with the grade of CaP. 26RFa stimulated the migration of native or transdifferentiated AI DU145 cells, but had no effect on their proliferation. Furthermore, 26RFa induced the neuroendocrine differentiation of DU145 cells as assessed by the occurrence of neurite-like extensions and the increase of the expression of the neuroendocrine marker chromogranin A.
The present data indicate that 26RFa may participate to the development of CaP at the AI state by promoting the neuroendocrine differentiation and the migration of cancer cells via autocrine/paracrine mechanisms.
越来越多的数据表明，神经内分泌细胞产生的神经肽在激素难治性前列腺癌（CaP）的进展和侵袭性中起着至关重要的作用。在这项研究中，我们研究了神经肽 26RFa 在 CaP 中的存在和功能。
我们定位并定量了 CaP 各等级切片中含有 26RFa 和其受体 GPR103 的肿瘤细胞。进行体外实验以研究 26RFa 对雄激素非依赖性（AI）前列腺癌细胞系 DU145 的迁移、增殖和神经内分泌分化的影响。
26RFa 和 GPR103 存在于表现出神经内分泌分化的癌灶中，并且 26RFa 和 GPR103 免疫反应性癌细胞的数量随着 CaP 的等级增加而增加。26RFa 刺激了天然或转分化的 AI DU145 细胞的迁移，但对其增殖没有影响。此外，26RFa 通过诱导神经元样突起的发生和神经内分泌标志物嗜铬粒蛋白 A 的表达增加，诱导 DU145 细胞的神经内分泌分化。
目前的数据表明，26RFa 可能通过自分泌/旁分泌机制促进癌细胞的神经内分泌分化和迁移，从而参与 AI 状态下 CaP 的发展。
