Distinct roles of small extracellular vesicles from resident and infiltrating macrophages on glioma growth and mobility

Previous studies revealed that tumor-associated macrophages/microglia (TAMs) promoted glioma invasiveness during tumor progression and after radiotherapy. However, the communication of TAMs with tumor cells remains unclear. This study aimed to examine the role of small extracellular vesicles (sEVs) derived from TAMs in TAMs-mediated brain tumor invasion. This study utilized BV2 and RAW264.7 cell lines representing resident and infiltrating macrophages, respectively, to unveil their effect on tumor cells. Purified sEVs from BV2 and RAW264.7 were validated by nanoparticle track analysis (NTA), transmission electron microscopy (TEM), and western blotting for sEV markers. The effect of sEVs on the murine astrocytoma tumor cell line ALTS1C1 was examined on cell proliferation, migration, and gene expression. The results showed that ALTS1C1 cells effectively engulfed sEVs purified from BV2 and RAW264.7. Only BV2-derived sEVs promoted cell proliferation and were dose-dependent. Further, morphological changes in ALTS1C1 cells were observed after incubation with BV2-derived sEVs, which was associated with enhancing cell migration. BV2-mediated glioma proliferation and mobility were related to the upregulation of vascular endothelial growth factor (VEGF) and downregulation of death effector domain-containing protein (DEDD) gene expression. This study demonstrates the distinct function of sEVs of resident macrophages on glioma cell invasion and reveals the mechanism underlying microglia-mediated tumor progression. These findings suggested resident microglia is the potential therapeutic target for TAMs-induced brain tumor invasiveness.