- 作者: Karine Varini, Amal Benzaria, Nadira Taieb, Coralie Di Scala, Amanda Azmi, Soraya Graoudi and Marc Maresca
- 作者服務機構: Interactions cellulaires neuroimmunes et pathologies du systeme nerveux central CRN2M, CNRS UMR 6231, University of Aix-Marseille 2 and Aix-Marseille 3, Faculte de Medecine - Secteur Nord, Universite de la Mediterranee, Marseille, France
- 中文摘要: --
- 英文摘要:
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.
- 中文關鍵字: --
- 英文關鍵字: Astrocytoma; Cancer; GLAST; GLT-1; Glutamate; EAAT; Mislocalization; STTG-1.