Hypoxic glioma-derived exosomes induce the activation of astrocytes by promoting autophagy

Abstract

Abstract The tumor microenvironment (TME) of glioma is formed by glioma cells and a series of surrounding cells, such as astrocytes, macrophages, T cells and neurons. In the TME, glioma cells can activate normal human astrocytes (NHAs) through the secretion of exosomes, and the activation of astrocytes can further improve the progression of glioma, leading to a poor prognosis for patients. However, the molecular mechanisms underlying glioma activation by NHAs are largely unknown.Here, we demonstrated that glioma-derived exosomes (GDEs) play an important role in the modulation of autophagy and activation of NHAs. Compared with normoxic glioma-derived exosomes (N-GDEs), hypoxic glioma-derived exosomes (H-GDEs) further improved autophagy and activation andstrongly promoted the proliferation and migration of glioma cells. In a miRNA array between two kinds of exosomes from glioma, we found that miR-423-3p was highly expressed in the H-GDEs, playedan important role in autophagy and resulted in the activation of NHAs. We identified the mechanism by which hypoxic glioma cells react with NHAsto create an immunosuppressive microenvironment. These findings provide new insight into the diagnosis and treatment of glioma by targeting autophagy or miR-423-3p.