10255-BOT-5 EXOSOMAL MIRNAS RELEASED FROM GLIOBLASTOMA CELLS AFTER BNCT TARGET CELL PROLIFERATION AND SURVIVAL SIGNALS

Abstract

Abstract Boron neutron capture therapy (BNCT) is a tumor -selective particle radiation therapy. In BNCT, p-boronophenyl alanine, which is actively taken up by tumor cells through LAT1 transporter, a member of the system L family of heterodimeric, sodium-independent, amino acid transporters, is administrated to patients, and thermal or epithermal neutron is irradiated to tumor tissue of the patients. Nuclear capture and fission reactions between boron-10 and thermal neutron occurred only in tumor cells produce high- linear energy transfer (LET) alpha particles and recoiling lithium-7 (7Li). These high LET particles have very short pathlength (5-9 μmeter), and kill boron-10 containing tumor cells sparing adjacent normal tissue cells. BNCT was applied to malignant glioma, the most devastating tumor and has prolonged the survival of malignant glioma patients. In this study, we comprehensively investigated the micro RNAs (miRNAs) in exosomes derived from BNCT-treated glioblastoma U87 MG cells using microarray. Comparing with non-treated cells, more than 300 up-regulated miRNAs or 100 down-regulated miRNAs were detected in BNCT-treated cells. From the results of the prediction analysis of the target genes which interact with the miRNAs, the pathway analysis was performed. We found significantly associated pathways, such as Focal adhesion-PI3K-Akt-mTOR, Ras, MAPK, etc. miRNAs in exosomes released from BNCT-treated glioblastoma cells may suppress such essential pathways for cell proliferation and survival.