McCoy Eric, Sontheimer Harald
Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Glia. 2007 Aug 1;55(10):1034-43. doi: 10.1002/glia.20524.
Aquaporins (AQP) constitute the principal pathway for water movement across biological membranes. Consequently, their expression and function is important for cell volume regulation. Glioma cells quickly adjust their cell volume in response to osmotic challenges or spontaneously as they invade into the narrow and tortuous extracellular spaces of the brain. These cell volume changes are likely to engage water movements across the cell membrane through AQP. AQP expression in glioma cells is poorly understood. In this study, we examined the expression of AQP in several commonly used human glioma cell lines (D54, D65, STTG1, U87, U251) and in numerous acute patient biopsies by PCR, Western blot, and immunocytochemistry and compared them to nonmalignant astrocytes and normal brain. All glioma patient biopsies expressed AQP1, AQP4 and some expressed AQP5. However, when isolated and grown as cell lines they lose all AQP proteins except a few cell lines that maintain expression of AQP1 (D65, U251, GBM62). Reintroducing either AQP1 or AQP4 stably into glioma cell lines allowed us to show that each AQP is sufficient to restore water permeability. Yet, only the presence of AQP1, but not AQP4, enhanced cell growth and migration, typical properties of gliomas, while AQP4 enhanced cell adhesion suggesting differential biological roles for AQP1 and AQP4 in glioma cell biology.
水通道蛋白（AQP）构成了水跨生物膜转运的主要途径。因此，它们的表达和功能对于细胞体积调节至关重要。胶质瘤细胞在应对渗透压挑战时会迅速调节其细胞体积，或者在侵入大脑狭窄且曲折的细胞外间隙时自发地调节细胞体积。这些细胞体积变化很可能涉及通过水通道蛋白的跨细胞膜水转运。目前对胶质瘤细胞中水通道蛋白的表达了解甚少。在本研究中，我们通过聚合酶链反应（PCR）、蛋白质免疫印迹法和免疫细胞化学检测了几种常用的人胶质瘤细胞系（D54、D65、STTG1、U87、U251）以及众多急性患者活检样本中水通道蛋白的表达，并将其与非恶性星形胶质细胞和正常脑组织进行比较。所有胶质瘤患者活检样本均表达水通道蛋白1（AQP1）、水通道蛋白4（AQP4），部分样本还表达水通道蛋白5（AQP5）。然而，当分离并培养成细胞系时，它们失去了所有水通道蛋白，只有少数细胞系（D65、U251、GBM62）维持水通道蛋白1的表达。将水通道蛋白1或水通道蛋白4稳定地重新导入胶质瘤细胞系后，我们发现每种水通道蛋白都足以恢复水通透性。然而，只有水通道蛋白1的存在，而不是水通道蛋白4，能增强细胞生长和迁移，这是胶质瘤的典型特性；而水通道蛋白4增强了细胞黏附，这表明水通道蛋白1和水通道蛋白4在胶质瘤细胞生物学中具有不同的生物学作用。
