Calatozzolo C, Salmaggi A, Pollo B, Sciacca F L, Lorenzetti M, Franzini A, Boiardi A, Broggi G, Marras C
Department of Neurology, Fondazione IRCCS Istituto Neurologico "C. Besta", Milan, Italy.
Neurol Sci. 2007 Dec;28(6):304-10. doi: 10.1007/s10072-007-0843-8. Epub 2008 Jan 4.
Recent studies have shown an anti-tumour activity of cannabinoid receptors CB1 and CB2 in gliomas. This effect was mediated by neurotrophins in breast and prostate carcinoma, while in gliomas this relationship has not yet been considered. The aim of this study was to investigate the expression of cannabinoid receptors CB1 and CB2, neurotrophin NGF and NT-3 and their receptors TrkA and TrkC in glioma and endothelial cells. The analysis was performed in 14 gliomas and 2 non-tumour brain specimens by immunohistochemistry and real-time quantitative-polymerase chain reaction (RTQ-PCR). Gliomas showed a weak immunoreactivity for CB1 and CB2 in tumour and in endothelial cells, and for NGF/TrkA mainly in tumour cells, while a moderate/diffuse immunoreactivity was found for NT-3/TrkC. CB2 was expressed on 3 out of 6 low-grade gliomas and in all high-grade gliomas. Non-tumour brain tissues were weakly positive in astrocytes and endothelium for CB1, CB2, NT-3 and TrkC and negative for NGF and TrkA. By RTQ-PCR, gliomas showed low mRNA levels of NGF/TrkA and moderate levels of CB1, NT-3 and TrkC. CB2 mRNA expression was low or absent. A potential role of cannabinoids, particularly of CB2 agonists devoid of psychotropic side effects, in glioma therapy could have a basis in glioblastomas, because they were all positive, though weakly, to CB2. The presence of neurotrophins and their receptors, mainly NT-3 and TrkC, suggests a possible role of these pathways in glioma growth/invasion, but further investigations are required to verify this hypothesis and a potential relationship between cannabinoids and neurotrophins.
近期研究表明,大麻素受体CB1和CB2在胶质瘤中具有抗肿瘤活性。在乳腺癌和前列腺癌中,这种效应是由神经营养因子介导的,而在胶质瘤中,这种关系尚未得到考虑。本研究的目的是调查大麻素受体CB1和CB2、神经营养因子NGF和NT-3及其受体TrkA和TrkC在胶质瘤和内皮细胞中的表达。通过免疫组织化学和实时定量聚合酶链反应(RTQ-PCR)对14例胶质瘤和2例非肿瘤性脑标本进行了分析。胶质瘤在肿瘤细胞和内皮细胞中对CB1和CB2显示出弱免疫反应性,对NGF/TrkA主要在肿瘤细胞中显示出弱免疫反应性,而对NT-3/TrkC则发现中度/弥漫性免疫反应性。CB2在6例低级别胶质瘤中的3例以及所有高级别胶质瘤中均有表达。非肿瘤性脑组织在星形胶质细胞和内皮细胞中对CB1、CB2、NT-3和TrkC呈弱阳性,对NGF和TrkA呈阴性。通过RTQ-PCR,胶质瘤显示出NGF/TrkA的低mRNA水平以及CB1、NT-3和TrkC的中度水平。CB2 mRNA表达低或缺失。大麻素,尤其是无精神副作用的CB2激动剂,在胶质瘤治疗中的潜在作用可能基于胶质母细胞瘤,因为它们对CB2均呈阳性,尽管较弱。神经营养因子及其受体的存在,主要是NT-3和TrkC,表明这些途径在胶质瘤生长/侵袭中可能发挥作用,但需要进一步研究来验证这一假设以及大麻素与神经营养因子之间的潜在关系。