Glutamate release promotes growth of malignant gliomas.
Glutamate neurotoxicity has been implicated in stroke, head trauma, multiple sclerosis and neurodegenerative diseases. Although recent data show that cultured glioma cells secrete glutamate, the growth potential of brain tumors has not yet been linked to an excitotoxic mechanism. Using bioluminescence detection of glutamate release from freshly prepared brain slices, we show that implanted glioma cells continue to secrete glutamate. Moreover, gliomas with high glutamate release have a distinct growth advantage in host brain that is not present in vitro. Treatment with the NMDA receptor antagonists MK801 or memantine slowed the growth of glutamate-secreting tumors in situ, suggesting that activation of NMDA receptors facilitates tumor expansion. These findings support a new approach for therapy of brain tumors, based upon antagonizing glutamate secretion or its target receptors.
Takano
T
T
Department of Cell Biology, Anatomy and Pathology, New York Medical College, Valhalla, New York, USA.
Lin
J H
JH
Arcuino
G
G
Gao
Q
Q
Yang
J
J
Nedergaard
M
M
D027322:Amino Acid Transport System X-AG; D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D002352:Carrier Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism*; D008163:Luminescent Measurements; D008297:Male; D008559:Memantine / Q000494:pharmacology; D009368:Neoplasm Transplantation; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D027981:Symporters; D014407:Tumor Cells, Cultured
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D018691:Excitatory Amino Acid Antagonists; D050491:Glutamate Plasma Membrane Transport Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D027981:Symporters; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D008559:Memantine