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Mislocalization of the exitatory amino-acid transporters (EAATs) in human astrocytoma and non-astrocytoma cancer cells: effect of the cell confluence.

Abstract

BACKGROUND
Astrocytomas are cancers of the brain in which high levels of extracellular glutamate plays a critical role in tumor growth and resistance to conventional treatments. This is due for part to a decrease in the activity of the glutamate transporters, i.e. the Excitatory Amino Acid Transporters or EAATs, in relation to their nuclear mislocalization in astrocytoma cells. Although non-astrocytoma cancers express EAATs, the localization of EAATs and the handling of L-glutamate in that case have not been investigated.
METHODS
We looked at the cellular localization and activity of EAATs in human astrocytoma and non-astrocytoma cancer cells by immunofluorescence, cell fractionation and L-glutamate transport studies.
RESULTS
We demonstrated that the nuclear mislocalization of EAATs was not restricted to astrocytoma and happened in all sub-confluent non-astrocytoma cancer cells we tested. In addition, we found that cell-cell contact caused the relocalization of EAATs from the nuclei to the plasma membrane in all human cancer cells tested, except astrocytoma.
CONCLUSIONS
Taken together, our results demonstrated that the mislocalization of the EAATs and its associated altered handling of glutamate are not restricted to astrocytomas but were also found in human non-astrocytoma cancers. Importantly, we found that a cell contact-dependent signal caused the relocalization of EAATs at the plasma membrane at least in human non-astrocytoma cancer cells, resulting in the correction of the altered transport of glutamate in such cancer cells but not in astrocytoma.

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    • Authors

    Varini K, Benzaria A, Taïeb N, Di Scala C, Azmi A, Graoudi S, Maresca M

    Institution

    InteractionsCellulaires Neuroimmunes et Pathologies du Système Nerveux Central, CRN2M, CNRS UMR 6231, University of Aix-Marseille 2 and Aix-Marseille 3, Faculté de Médecine-Secteur Nord, Université de la Méditerranée, Marseille, France.

    Source

    Journal of biomedical science 19: 2012 pg 10

    MeSH

    Amino Acid Transport System X-AG
    Amino Acid Transport Systems
    Astrocytes
    Astrocytoma
    Biological Transport
    Blotting, Western
    Cell Fractionation
    Cell Line, Tumor
    Glutamic Acid
    Humans
    Microscopy, Fluorescence
    Neoplasms

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    22296701