EXOSOMES DERIVED FROM GLIOMA STEM CELLS (GSCS) PROMOTE CELL MIGRATION, PROLIFERATION AND RADIATION RESISTANCE IN BRAIN CANCER

Introduction: Glioblastoma is the most common brain tumour with 15 month median survival due to rapid recurrence and metastasis after initial treatment. Accumulating evidences demonstrated Glioma Stem Cells (GSCs) play a vital role in tumour metastasis and therapeutic resistance but the molecular mechanism remains unclear. This study aims to identify the roles of GSCs-derived exosomes in tumour cell progression and radiation resistance to promote metastasis. Materials and Methods: Exosomes were isolated from GSCs (GSCs-Exos) by serial centrifugation. Exosomes size and morphology were confirmed using Nanosight measurement and transmission electron microscopy respectively. Differentiated glioma cell lines LN229 and U118 were utilized as recipient cell model. LN229 and U118 cells were treated with and without GSCs-Exos and their functions studied. Wound healing and spheroid migration assays were performed to detect cell migration. We also employed cell viability assay to detect cell proliferation. Colony formation assay were conducted to detect the cell survival of irradiated recipient cells after exposed to GSCs-Exos. Results: Transmission electron microscopy and Nanosight demonstrated GSCs can produce exosomes into microenvironment. Both LN229 and U118 cells increased their migratory ability in the presence of GSCs-Exos. When LN229 and U118 were exposed to GSCs-Exos, there was an increase in cell proliferation. Radiation efficacy of LN229 and U118 reduced significantly by GSCs-Exos and induced colony formation compared to differentiated glioma cells-derived exosomes. CONCLUSION: Our study showed exosomes are released by GSCs and can be taken up by differentiated glioma cells. In the presence of GSCs-Exos, differentiated glioma cells have higher proliferation and migration capacity, and acquire resistance of traditional therapeutic radiation. These results indicated GSCs-Exos play an important role in tumour progression and metastasis after conventional therapeutics. Future study will be focused on GSCs-Exos cargo content for potential prognosis biomarker identification.