Expression of glutamate receptor subunits in pediatric brain tumors

Abstract

Introduction: Glutamate is an important excitatory neurotransmitter in the mammalian brain. It activates ionotropic and metabotropic receptors. Experimental evidence demonstrates that glutamate receptor antagonists limit tumor growth and suggests that subtypes of glutamate receptors may differentially regulate proliferation of brain tumors: While the expression of mGlu4-receptors is inversely related to spreading and recurrence of human medulloblastoma, blockage of the calcium permeable AMPA receceptors leads to apoptosis in human glioblastoma. Results: The present study aimed at exploring the expression profile of ionotropic and metabotropic glutamate receptor subunits in pediatric brain tumors. Tissue samples from eight ependymomas, four glioblastomas, sechs medulloblastomas and nine astrocytomas were analysed regarding their expression of NMDA receptor subunits NR1-NR3b, AMPA/kainate receptor subunits GluR1-GluR7, kainate receptor subunits KA1 und KA2 as well as metabotropic receptor subunits mGluR1-mGluR8. RNA was obtained from tumor-derived tissue and used for RT-PCR followed by polyacrylamide gel electrophoresis. Sections of paraffin-embedded tumor samples were analyzed by immunohistochemistry. The expression of the different subunits was variable depending on the tumor type, but for NR1 we detected a decreased and for GluR5 an increased or stable expression in nearly all of the samples. Summary: About 20% of all malignancies in children are primary CNS-tumors. This study demonstrates different expression patterns of glutamate receptor subunits in different histological CNS-tumor entities of pediatric patients. An expansion of this project including a larger number of tumor samples is planned. Together with the experimental evidence indicating that interference with glutamate signalling may suppress tumor growth, our findings suggest that adjunctive treatment with glutamate receptor antagonists may indeed be a feasible future therapeutic option for pediatric patients with brain tumors which should be explored further.