Oshio Kotaro, Binder Devin K, Liang Yu, Bollen Andrew, Feuerstein Burt, Berger Mitchel S, Manley Geoffrey T
Department of Neurological Surgery, University of California, San Francisco, San Francisco, California, USA.
Neurosurgery. 2005 Feb;56(2):375-81; discussion 375-81. doi: 10.1227/01.neu.0000148904.57841.6b.
Malignant glial tumors are associated with cerebral edema. The aquaporins (AQPs) are a family of membrane proteins that provide a major pathway for water transport in mammals. In the central nervous system, AQP1 is selectively expressed in the choroid plexus and thought to participate in cerebrospinal fluid production. Prior studies have suggested that AQP1 may be up-regulated in glial tumors, potentially contributing to tumor-associated edema. The objective of this study was to investigate the expression of AQP1 in a large series of human glial tumors.
Thirty-six human glial tumors were obtained from the University of California, San Francisco Neurosurgery Tissue Bank. AQP1 expression was evaluated by reverse transcriptase polymerase chain reaction, complementary deoxyribonucleic acid gene array, Western blot analysis, and immunohistochemical analyses.
AQP1, normally restricted to choroid epithelia, was highly expressed in glioblastomas. Complementary deoxyribonucleic acid array, Western blot analysis, and immunohistochemical analysis revealed intense up-regulation of AQP1 expression in all glioblastomas studied.
The abnormal up-regulation of AQP1 in glial tumors suggests a potential pathological role for this membrane water channel and raises the possibility that selective AQP1 inhibition might offer a new therapeutic target for treatment of tumor-associated edema.
恶性胶质肿瘤与脑水肿相关。水通道蛋白(AQPs)是一类膜蛋白家族,为哺乳动物体内水的运输提供了主要途径。在中枢神经系统中,AQP1在脉络丛中选择性表达,并被认为参与脑脊液的生成。先前的研究表明,AQP1可能在胶质肿瘤中上调,这可能导致肿瘤相关的水肿。本研究的目的是调查大量人类胶质肿瘤中AQP1的表达情况。
从加利福尼亚大学旧金山分校神经外科组织库获取36例人类胶质肿瘤。通过逆转录聚合酶链反应、互补脱氧核糖核酸基因芯片、蛋白质免疫印迹分析和免疫组织化学分析评估AQP1的表达。
AQP1通常局限于脉络丛上皮,在胶质母细胞瘤中高表达。互补脱氧核糖核酸芯片、蛋白质免疫印迹分析和免疫组织化学分析显示,在所研究的所有胶质母细胞瘤中,AQP1表达均显著上调。
胶质肿瘤中AQP1的异常上调表明该膜水通道具有潜在的病理作用,并增加了选择性抑制AQP1可能为治疗肿瘤相关水肿提供新治疗靶点的可能性。