Glutamate receptors in pediatric tumors of the central nervous system.
Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system (CNS). Experimental evidence indicates that glutamate receptor antagonists may limit tumor growth. This study explores expression of glutamate receptor subunits in pediatric CNS tumors. Samples from eight ependymomas, four glioblastomas, six medulloblastomas and eight low grade astrocytomas were analysed. RNA was used for semiquantitative and quantitative RT-PCR. We examined expression of NMDA receptor subunits NR1-NR3B, AMPA receptor subunits GluR1-GluR4, kainate receptor subunits GluR5-GluR7, KA1, KA2 and metabotropic receptor subunits mGluR1-8. Paraffin embedded samples were immunohistochemically stained for selected subunits. All glutamate receptor subunits were differentially expressed in the tumors examined. Expression of NR2D, NR3A, KA1, GluR4, mGluR1, mGluR4, mGluR5 and mGluR6 was higher in the high grade tumors compared to human brain (HB). In low grade astrocytomas expression of glutamate receptor subunits was comparable or lower than in HB. Immunohistochemistry revealed expression of several glutamate receptor subunit proteins in tumor specimen. This study demonstrates expression of glutamate receptor subunits in pediatric CNS tumors. Together with experimental evidence indicating that interference with glutamate signalling may suppress tumor growth, our findings suggest that adjunctive treatment with glutamate receptor modulators may be a feasible therapeutic option for pediatric patients with CNS tumors.
Brocke
Katja S
KS
Department of Pediatric Neurology, University Hospital Carl Gustav Carus, Children's Hospital, University of Technology Dresden, Dresden, Germany.
Staufner
Christian
C
Luksch
Hella
H
Geiger
Kathrin D
KD
Stepulak
Andrzej
A
Marzahn
Jenny
J
Schackert
Gabriele
G
Temme
Achim
A
Ikonomidou
Chrysanthy
C
D001921:Brain / Q000378:metabolism; D002490:Central Nervous System / Q000737:chemistry / Q000378:metabolism; D002648:Child; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D005971:Glutamates / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018092:Kainic Acid Receptors / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D018377:Neurotransmitter Agents; D021122:Protein Subunits; D064529:Receptor, Metabotropic Glutamate 5; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C578935:GRM5 protein, human; C409466:NR1 NMDA receptor; C113897:metabotropic glutamate receptor 6; C104077:metabotropic glutamate receptor type 1; C108823:metabotropic glutamate receptor 4