HGG-14. IRRADIATION OF PEDIATRIC GLIOBLASTOMA CELLS INDUCES DOWNREGULATION OF TUMOR SUPPRESSOR MICRORNA GENES AND UPREGULATION OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF). Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Alhajala, Hisham; Doan, Ninh; Al-Gizawiy, Mona; Knipstein, Jeffrey; Schmainda, Kathleen; Chitambar, Cristopher
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i91
• Page End: i91
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.286
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: INTRODUCTION: Recurrent glioblastoma (GBM) is known to be more aggressive and resistant to therapy when compared to the de-novo GBM tumor. Our previous in vivo studies showed that irradiated SJ-GBM2 cells exhibit greater radiological differences in angiogenesis and biological aggressiveness when compared with untreated (control) SJ-GBM2 cells. This may be explained by biological changes that occur after treatment with radiation and chemotherapy. Herein, we present evidence of changes in 21 gene expression and invasion protein markers between irradiated and non-irradiated cells. METHODS: Pediatric GBM cells (SJ-GBM2) were irradiated with a total dose of 10Gy (SJGBM2-10gy). Irradiated and untreated control cells were tested for viability and changes in microRNA (miRNA) expression using miRNA microarrays that analyze more than 2000 genes. Samples were analyzed in duplicate. Western blots of the irradiated and control cell lysates and dot blots of the cell conditioned serum-free media were immunostained for pro-cathepsin B and VEGF. RESULTS: Only a relatively small set of miRNAs exhibited differential expression; 21 miRNAs genes were downregulated and none were upregulated in SJGBM2-10gy compared with SJ-GBM2 cells. Many of these down-regulated miRNAs were found to be tumor suppressor genes. This study also identified multiple novel downregulated miRNAs that have not yet been characterized. VEGF secretion was increased in the irradiated cells. DISCUSSION: Our study demonstrates increased biological aggressiveness in irradiated SJGBM2-10gy cells and suggests that this is due to multiple mechanisms that are activated following irradiation. These mechanisms include down-regulation of tumor suppressors' miRNA genes and changes in the secretion of VEGF.