Regulation and function of aquaporin-1 in glioma cells
Regulation and function of aquaporin-1 in glioma cells
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DOI：
10.1593/neo.07454
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发表时间：
2007-09-01
期刊：
影响因子：
4.8
通讯作者：
Merrill, Marsha J.
中科院分区：
文献类型：
--
作者：
Hayashi, Yasuhiko;Edwards, Nancy A.;Merrill, Marsha J.
与正常脑组织相比，多形性胶质母细胞瘤表达水通道蛋白(AQP)1。水通道蛋白可能促进细胞的水肿、运动，以及水和H+从细胞内到细胞外的穿梭。我们试图深入了解AQP1在GBM中的功能。在培养的9L胶质肉瘤细胞中，地塞米松、血小板衍生生长因子、氯化钠、低氧、D-葡萄糖(而不是L-葡萄糖)和果糖都能诱导AQP1的表达。AQP1表达的诱导与糖酵解水平相关，通过增加D-葡萄糖或果糖和降低O2而达到最大，并通过测量乳酸脱氢酶(LDH)活性和介质乳酸浓度来定量。在糖酵解条件下培养的9L细胞中也观察到组织蛋白酶B的上调。免疫组织化学染色显示AQP1、LDH和组织蛋白酶B在与肿瘤周围血管相关的胶质瘤细胞中表达增加。已知的是，基底膜表现出有氧糖酵解。肿瘤周围葡萄糖代谢增加可能导致AQP1、LDH和组织蛋白酶B表达上调，从而导致细胞外环境酸化和胶质瘤细胞在血管周围空间的侵袭潜能。AQP1在胶质瘤中上调和代谢的特殊后果可能提供一个治疗靶点，既作为细胞表面标志物，也作为功能干预。
Glioblastoma multiformes ( GBMs) express increased aquaporin ( AQP) 1 compared to normal brain. AQPs may contribute to edema, cell motility, and shuttling of H2O and H+ from intracellular to extracellular space. We sought to gain insight into AQP1 function in GBM. In cultured 9L gliosarcoma cells, AQP1 expression was induced by dexamethasone, platelet-derived growth factor, NaCl, hypoxia, D-glucose ( but not L-glucose), and fructose. Induction of AQP1 expression correlated with the level of glycolysis, maximized by increasing medium D-glucose or fructose and decreasing O-2, and was quantified by measuring lactate dehydrogenase ( LDH) activity and medium lactate concentration. Upregulation of the protease cathepsin B was also observed in 9L cells cultured under glycolytic conditions. Immunohistochemical staining of human GBM specimens revealed increased coincident expression of AQP1, LDH, and cathepsin B in glioma cells associated with blood vessels at the tumor periphery. GBMs are known to exhibit aerobic glycolysis. Increased glucose metabolism at the tumor periphery may provide a scenario by which upregulation of AQP1, LDH, and cathepsin B contributes to acidification of the extracellular milieu and to invasive potential of glioma cells in perivascular space. The specific upregulation and metabolic consequences of increased AQP1 in gliomas may provide a therapeutic target, both as a cell surface marker and as a functional intervention.