Regulation and function of aquaporin-1 in glioma cells.
Glioblastoma multiformes (GBMs) express increased aquaporin (AQP) 1 compared to normal brain. AQPs may contribute to edema, cell motility, and shuttling of H(2)O 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.
Hayashi
Yasuhiko
Y
Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892, USA.
Edwards
Nancy A
NA
Proescholdt
Martin A
MA
Oldfield
Edward H
EH
Merrill
Marsha J
MJ
D000332:Aerobiosis; D000818:Animals; D051398:Aquaporin 1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D001932:Brain Neoplasms / Q000378:metabolism / Q000473:pathology*; D002401:Cathepsin B / Q000096:biosynthesis / Q000235:genetics; D015687:Cell Hypoxia; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D018316:Gliosarcoma / Q000378:metabolism / Q000473:pathology*; D006019:Glycolysis; D006601:Hexoses / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis / Q000235:genetics; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051381:Rats; D020218:Response Elements
C496022:Aqp1 protein, rat; D016895:Culture Media, Serum-Free; D006601:Hexoses; D009363:Neoplasm Proteins; D051398:Aquaporin 1; D007770:L-Lactate Dehydrogenase; D002401:Cathepsin B