title: 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.
authors.affiliation: 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.
authors.forename: Karine
authors.initials: K
authors.lastname: Varini
authors.forename: Amal
authors.initials: A
authors.lastname: Benzaria
authors.forename: Nadira
authors.initials: N
authors.lastname: Taïeb
authors.forename: Coralie
authors.initials: C
authors.lastname: Di Scala
authors.forename: Amanda
authors.initials: A
authors.lastname: Azmi
authors.forename: Soraya
authors.initials: S
authors.lastname: Graoudi
authors.forename: Marc
authors.initials: M
authors.lastname: Maresca
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism*; D026905:Amino Acid Transport Systems / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism*; D001692:Biological Transport; D015153:Blotting, Western; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D009369:Neoplasms / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D026905:Amino Acid Transport Systems; D018698:Glutamic Acid