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Expression of glutamate receptor subunits in human cancers |
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| Authors: | Andrzej Stepulak Hella Luksch Christine Gebhardt Ortrud Uckermann Jenny Marzahn Marco Sifringer Wojciech Rzeski Christian Staufner Katja S. Brocke Lechoslaw Turski Chrysanthy Ikonomidou |
| Affiliation: | 1. Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093, Lublin, Poland 2. Department of Pediatric Neurology, Medical Faculty Carl Gustav Carus, Children’s Hospital, University of Technology Dresden, Fetscherstrasse 74, 01307, Dresden, Germany 3. Institute of Neurophysiology, Charité, Humboldt University, Berlin, Germany 4. Department of Anaesthesiology and Intensive Care Medicine, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Augustenburger Platz 1, 13353, Berlin, Germany 5. Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, 20-033, Lublin, Poland 6. Department of Medical Biology, Institute of Agricultural Medicine, 20-950, Lublin, Poland 7. Solvay Pharmaceuticals Research Laboratories, C.J. van Houtenlaan 36, 1392 CP, Weesp, The Netherlands 8. Department of Neurology & Waisman Center, University of Wisconsin, Madison, WI, USA 9. Department of Neurology, H6/574 Clinical Science Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenus, Madison, WI, 53792, USA |
| Abstract: | Emerging evidence suggests a role for glutamate and its receptors in the biology of cancer. This study was designed to systematically analyze the expression of ionotropic and metabotropic glutamate receptor subunits in various human cancer cell lines, compare expression levels to those in human brain tissue and, using electrophysiological techniques, explore whether cancer cells respond to glutamate receptor agonists and antagonists. Expression analysis of glutamate receptor subunits NR1-NR3B, GluR1-GluR7, KA1, KA2 and mGluR1-mGluR8 was performed by means of RT-PCR in human rhabdomyosarcoma/medulloblastoma (TE671), neuroblastoma (SK-NA-S), thyroid carcinoma (FTC 238), lung carcinoma (SK-LU-1), astrocytoma (MOGGCCM), multiple myeloma (RPMI 8226), glioma (U87-MG and U343), lung carcinoma (A549), colon adenocarcinoma (HT 29), T cell leukemia cells (Jurkat E6.1), breast carcinoma (T47D) and colon adenocarcinoma (LS180). Analysis revealed that all glutamate receptor subunits were differentially expressed in the tumor cell lines. For the majority of tumors, expression levels of NR2B, GluR4, GluR6 and KA2 were lower compared to human brain tissue. Confocal imaging revealed that selected glutamate receptor subunit proteins were expressed in tumor cells. By means of patch-clamp analysis, it was shown that A549 and TE671 cells depolarized in response to application of glutamate agonists and that this effect was reversed by glutamate receptor antagonists. This study reveals that glutamate receptor subunits are differentially expressed in human tumor cell lines at the mRNA and the protein level, and that their expression is associated with the formation of functional channels. The potential role of glutamate receptor antagonists in cancer therapy is a feasible goal to be explored in clinical trials. |
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