Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment

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Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment

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Title: Attenuated AMPA Receptor Expression Allows Glioblastoma Cell Survival in Glutamate-Rich Environment
Author: van Vuurden, Dannis G.; Yazdani, Maryam; Bosma, Ingeborg; Broekhuizen, Aart J. F.; Postma, Tjeerd J.; Heimans, Jan J.; van der Valk, Paul; Aronica, Eleonora; Würdinger, Thomas; Kaspers, Gertjan J. L.; Cloos, Jacqueline; Tannous, Bakhos A.

Note: Order does not necessarily reflect citation order of authors.

Citation: van Vuurden, Dannis G., Maryam Yazdani, Ingeborg Bosma, Aart J. F. Broekhuizen, Tjeerd J. Postma, Jan J. Heimans, Paul van der Valk, et al. 2009. Attenuated AMPA receptor expression allows glioblastoma cell survival in glutamate-rich environment. PLoS ONE 4(6): e5953.
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Abstract: Background: Glioblastoma multiforme (GBM) cells secrete large amounts of glutamate that can trigger AMPA-type glutamate receptors (AMPARs). This commonly results in Na+ and Ca2+-permeability and thereby in excitotoxic cell death of the surrounding neurons. Here we investigated how the GBM cells themselves survive in a glutamate-rich environment. Methods and Findings: In silico analysis of published reports shows down-regulation of all ionotropic glutamate receptors in GBM as compared to normal brain. In vitro, in all GBM samples tested, mRNA expression of AMPAR subunit GluR1, 2 and 4 was relatively low compared to adult and fetal total brain mRNA and adult cerebellum mRNA. These findings were in line with primary GBM samples, in which protein expression patterns were down-regulated as compared to the normal tissue. Furthermore, mislocalized expression of these receptors was found. Sequence analysis of GluR2 RNA in primary and established GBM cell lines showed that the GluR2 subunit was found to be partly unedited. Conclusions: Together with the lack of functional effect of AMPAR inhibition by NBQX our results suggest that down-regulation and afunctionality of AMPARs, enable GBM cells to survive in a high glutamate environment without going into excitotoxic cell death themselves. It can be speculated that specific AMPA receptor inhibitors may protect normal neurons against the high glutamate microenvironment of GBM tumors.
Published Version: doi:10.1371/journal.pone.0005953
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2693929/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:4728513

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