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BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells

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Abstract

Medulloblastoma is the most common brain tumor of childhood. Emerging molecular targets in medulloblastoma include neurotrophin and neuropeptide receptors. In the present study, we have examined the influence of brain-derived neurotrophic factor (BDNF)/TrkB receptor- and gastrin-releasing peptide receptor (GRPR)-mediated signaling on the viability of human medulloblastoma cells. The expression of TrkB and GRPR was confirmed by immunohistochemistry and mRNA for both BDNF and GRPR was detected by reverse transcriptase polymerase chain reaction in Daoy, D283, and ONS76 cells. Treatment with BDNF significantly inhibited the viability of Daoy and D283, but not ONS76 cells, measured with the MTT assay. Neither the GRPR agonists GRP and bombesin nor the GRPR antagonist RC-3095 affected cell viability. Because previous findings have indicated that the viability of glioma cells might be enhanced by GRP when combined with the cAMP phosphodiesterase-4 (PDE4) inhibitor rolipram, we also examined the effects of rolipram alone or combined with GRP on cell viability. Rolipram significantly reduced the viability of all three cell lines, and the inhibitory effect of rolipram in Daoy cells was not modified by cotreatment with GRP. The results suggest that BDNF/TrkB and PDE4, but not the GRPR, regulate the viability of medulloblastoma cells.

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Acknowledgements

This research was supported by the National Council for Scientific and Technological Development (CNPq; Brazil) grant 301578/2006-0 to R.R.; the South American Office for Anticancer Drug Development (SOAD; Porto Alegre, Brazil); the Children's Cancer Institute (ICI-RS; Porto Alegre, Brazil); and the National Institute for Translational Medicine (INCT program). The authors thank Dr. Michael D. Taylor for his kind donation of the medulloblastoma cell lines.

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Authors and Affiliations

  1. Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, Rua Sarmento Leite, 2350, 90035-003, Porto Alegre, RS, Brazil

    Anna Laura Schmidt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Gilberto Schwartsmann, Algemir Lunardi Brunetto & Rafael Roesler

  2. National Institute for Translational Medicine (INCT-TM), 90035-003, Porto Alegre, RS, Brazil

    Anna Laura Schmidt, Caroline Brunetto de Farias, Ana Lucia Abujamra, Flávio Kapczinski, Gilberto Schwartsmann, Algemir Lunardi Brunetto & Rafael Roesler

  3. Children’s Cancer Institute (ICI-RS) and Pediatric Oncology Service, 90035-003, Porto Alegre, RS, Brazil

    Caroline Brunetto de Farias, Ana Lucia Abujamra & Algemir Lunardi Brunetto

  4. Laboratory of Molecular Psychiatry, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Flávio Kapczinski

  5. Department of Internal Medicine, Faculty of Medicine, Federal University of Rio Grande do Sul, 90035-003, Porto Alegre, RS, Brazil

    Gilberto Schwartsmann

  6. Laboratory of Molecular Neuropharmacology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90046-900, Porto Alegre, RS, Brazil

    Rafael Roesler

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  1. Anna Laura Schmidt
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Correspondence to Rafael Roesler.

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Schmidt, A.L., de Farias, C.B., Abujamra, A.L. et al. BDNF and PDE4, but not the GRPR, Regulate Viability of Human Medulloblastoma Cells. J Mol Neurosci 40, 303–310 (2010). https://doi.org/10.1007/s12031-009-9221-8

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  • DOI: https://doi.org/10.1007/s12031-009-9221-8

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