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Expression of glutamate receptor subunits in human cancers

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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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Acknowledgment

The work was supported by Deutsche Forschungsgemeinschaft grant IK2/6-1.

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, Medical University of Lublin, 20-093, Lublin, Poland

    Andrzej Stepulak

  2. Department of Pediatric Neurology, Medical Faculty Carl Gustav Carus, Children’s Hospital, University of Technology Dresden, Fetscherstrasse 74, 01307, Dresden, Germany

    Andrzej Stepulak, Hella Luksch, Ortrud Uckermann, Jenny Marzahn, Christian Staufner, Katja S. Brocke & Chrysanthy Ikonomidou

  3. Institute of Neurophysiology, Charité, Humboldt University, Berlin, Germany

    Christine Gebhardt

  4. Department of Anaesthesiology and Intensive Care Medicine, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Augustenburger Platz 1, 13353, Berlin, Germany

    Marco Sifringer

  5. Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Sklodowska University, 20-033, Lublin, Poland

    Wojciech Rzeski

  6. Department of Medical Biology, Institute of Agricultural Medicine, 20-950, Lublin, Poland

    Wojciech Rzeski

  7. Solvay Pharmaceuticals Research Laboratories, C.J. van Houtenlaan 36, 1392 CP, Weesp, The Netherlands

    Lechoslaw Turski

  8. Department of Neurology & Waisman Center, University of Wisconsin, Madison, WI, USA

    Chrysanthy Ikonomidou

  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

    Chrysanthy Ikonomidou

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  1. Andrzej Stepulak
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  2. Hella Luksch
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  7. Wojciech Rzeski
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  8. Christian Staufner
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  9. Katja S. Brocke
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  10. Lechoslaw Turski
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  11. Chrysanthy Ikonomidou
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Correspondence to Chrysanthy Ikonomidou.

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Stepulak, A., Luksch, H., Gebhardt, C. et al. Expression of glutamate receptor subunits in human cancers. Histochem Cell Biol 132, 435–445 (2009). https://doi.org/10.1007/s00418-009-0613-1

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  • DOI: https://doi.org/10.1007/s00418-009-0613-1

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