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

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. © 2012 varini et al; licensee biomed central ltd.