Abstract
Glioblastoma multiforme is the most undifferentiated type of brain tumor, and its prognosis is extremely poor. Glioblastoma cells exhibit highly migratory and invasive behavior, which makes surgical intervention unsuccessful. Here, we showed that glioblastoma cells express Ca(2+)-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors assembled from the GluR1 and/or GluR4 subunits, and that their conversion to Ca(2+)-impermeable receptors by adenovirus-mediated transfer of the GluR2 cDNA inhibited cell locomotion and induced apoptosis. In contrast, overexpression of Ca(2+)-permeable AMPA receptors facilitated migration and proliferation of the tumor cells. These findings indicate that Ca(2+)-permeable AMPA receptors have crucial roles in growth of glioblastoma. Blockage of these Ca(2+)-permeable receptors may be a useful therapeutic strategy for the prevention of glioblastoma invasion.
MeSH terms
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Adenoviridae / genetics
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Animals
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Apoptosis
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Brain Neoplasms / drug therapy
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Brain Neoplasms / metabolism
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Brain Neoplasms / pathology*
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Calcium / metabolism
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Cell Movement / genetics
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Genetic Vectors / pharmacology
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Glioblastoma / drug therapy
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Glioblastoma / metabolism
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Glioblastoma / pathology*
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Humans
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Imidazoles / pharmacology
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Mice
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Mice, Nude
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Permeability
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Quinoxalines / pharmacology
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Receptors, AMPA / antagonists & inhibitors*
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Receptors, AMPA / drug effects
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Receptors, AMPA / genetics
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Receptors, AMPA / metabolism
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Tumor Cells, Cultured
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / metabolism
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / pharmacology
Substances
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Imidazoles
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Quinoxalines
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Receptors, AMPA
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glutamate receptor ionotropic, AMPA 4
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2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
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YM 872
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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glutamate receptor ionotropic, AMPA 2
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Calcium
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glutamate receptor ionotropic, AMPA 1