Schley Marcus, Ständer Sonja, Kerner John, Vajkoczy Peter, Schüpfer Guido, Dusch Martin, Schmelz Martin, Konrad Christoph
Department of Anaesthesiology and Operative Intensive Care, Kantonsspital Lucerne, CH-6000 Lucerne 16, Switzerland.
Brain Res Bull. 2009 Jun 30;79(5):333-7. doi: 10.1016/j.brainresbull.2009.01.011. Epub 2009 Feb 6.
The most abundant malignant brain tumor in human is glioblastoma and patients with this type of tumor have a poor prognosis with high mortality. Glioblastoma are characterized particularly by fast growth and a dependence on blood vessel formation for survival. Cannabinoids (CBs) inhibit tumor growth by inducing apoptosis of tumor cells and impairing tumor angiogenesis. The distribution of CB1 and CB2 receptors in glioblastoma and associated endothelial vessels is still unknown.
Tissue samples were collected consecutively after neurosurgery of 19 patients suspected glioblastoma and examined immunohistochemically for CB1 and CB2 receptor expression. Vessel endothelial cells of the sections were immunocytochemically identified by using a primary antibody against PECAM-1. Double labelling was performed for CB receptors and endothelial cells of the vessels by DAPI staining.
In endothelia of control tissue, about 24% and 45% of the cells were positive for CB1 and CB2 receptors. In glioblastoma endothelial cells, CB1 and CB2 receptors were present in about 38% and 54% of the cells respectively. In comparison to CB1, an elevated CB2 receptor expression was identified in glioblastoma.
The abundant expression and distribution of CB2 receptors in glioblastoma and particularly endothelial cells of glioblastoma indicate that impaired tumor growth in presence of CB may be associated with CB2 activation. Selective CB2 agonists might become important targets attenuating vascular endothelial growth factor (VEGF) signalling and thereby diminishing neoangiogenesis and glioblastoma growth.
人类最常见的恶性脑肿瘤是胶质母细胞瘤,这类肿瘤患者预后较差,死亡率高。胶质母细胞瘤的特点尤其在于生长迅速且依赖血管生成来维持生存。大麻素(CBs)通过诱导肿瘤细胞凋亡和抑制肿瘤血管生成来抑制肿瘤生长。胶质母细胞瘤及相关内皮血管中CB1和CB2受体的分布仍不清楚。
连续收集19例疑似胶质母细胞瘤患者神经外科手术后的组织样本,免疫组化检测CB1和CB2受体表达。切片的血管内皮细胞通过使用抗PECAM-1一抗进行免疫细胞化学鉴定。通过DAPI染色对血管的CB受体和内皮细胞进行双重标记。
在对照组织的内皮细胞中,约24%和45%的细胞CB1和CB2受体呈阳性。在胶质母细胞瘤内皮细胞中,CB1和CB2受体分别存在于约38%和54%的细胞中。与CB1相比,胶质母细胞瘤中CB2受体表达升高。
CB2受体在胶质母细胞瘤尤其是胶质母细胞瘤内皮细胞中的丰富表达和分布表明,在存在CB的情况下肿瘤生长受抑制可能与CB2激活有关。选择性CB2激动剂可能成为减弱血管内皮生长因子(VEGF)信号传导从而减少新生血管生成和胶质母细胞瘤生长的重要靶点。