Hélène Ipas, Audrey Guttin and Jean-Paul Issartel Pages 131 - 145 ( 15 )
Brain glial tumors, and particularly glioblastomas, are tumors with a very poor prognosis. Currently, the parameters that control aggressiveness, migration, or chemoresistance are not well known. In this tumor context, microRNAs are thought to be essential actors of tumorigenesis as they are able to control the expression of numerous genes. microRNAs are not only active in controlling tumor cell pathways, they are also secreted by cells, inside microvesicles called exosomes, and may play specific roles outside the tumor cells in the tumor microenvironment. We analyzed the microRNA content of exosomes produced in vitro by normal glial cells (astrocytes) and tumor glial cells (U87 MG) using Affymetrix microarrays. It appears that the exosome microRNA profiles are qualitatively quite similar. Nevertheless, their quantitative profiles are different and may be potentially taken as an opportunity to carry out assays of diagnostic interest. We submitted the cultured cells to several stresses such as oxygen deprivation or treatments with chemical drugs (GW4869 or 5-Aza-2’- deoxycitidine) to assess the impact of the cellular microRNA profile modifications on the exosome microRNA profiles. We found that modifications of the cellular microRNA content are not strictly mirrored in exosomes. On the basis of these results, we propose that the way microRNAs are released in exosomes is probably the result of a combination of different excretion mechanisms or constraints that concur in a controlled regulation of the exosome microRNA secretion.
Astrocyte, exosome, glioblastoma, hypoxia, microarray, microRNA.
Grenoble Institut des Neurosciences, Chemin Fortuné Ferrini, F-38000 Grenoble, France.