CD133 positive U87 glioblastoma cells-derived exosomal microRNAs in hypoxia- versus normoxia-microenviroment

Abstract

Hypoxia is a major regulator of glioma development and aggressiveness. However, how CD133 positive U87 glioblastoma cells adapt to hypoxia and communicate with their surrounding microenvironment during tumor development remain important questions. Communication with host cells and stroma via exosomes represents one pathway by which tumors can modify their surroundings to achieve a tumor-permissive environment. MicroRNAs are thought to be essential actors of tumorigenesis as they are able to control the expression of numerous genes. Here, we show that exosomes derived from CD133+ U87 glioblastoma cells grown at hypoxic compared with normoxic conditions are potent proliferation inducers of the tumor vasculature and glioma cells proliferation in vitro. Moreover, we analyze the microRNA content of exosomes produced in vitro by hypoxia and normoxia CD133+ U87 glioblastoma cells 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 conclude that CD133+ U87 glioblastoma cells derived exosome-mediated miRNA transduction play an important role of mediating a proangiogenic response and glioma cells proliferation, and that the exosomal pathway constitutes a potentially targetable driver of hypoxia-dependent intercellular signaling during tumor development.

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