Irradiation of pediatric glioblastoma cells promotes radioresistance and enhances glioma malignancy via genome-wide transcriptome changes. Oncotarget 2018 Sep 25;9(75):34122-34131
Date
10/23/2018Pubmed ID
30344926Pubmed Central ID
PMC6183347DOI
10.18632/oncotarget.26137Scopus ID
2-s2.0-85053940800 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
Pediatric glioblastoma (GBM) is a relatively rare brain tumor in children that has a dismal prognosis. Surgery followed by radiotherapy is the main treatment protocol used for older patients. The benefit of adjuvant chemotherapy is still limited due to a poor understanding of the underlying molecular and genetic changes that occur with irradiation of the tumor. In this study, we performed total RNA sequencing on an established stable radioresistant pediatric GBM cell line to identify mRNA expression changes following radiation. The expression of many genes was altered in the radioresistant pediatric GBM model. These genes have never before been reported to be associated with the development of radioresistant GBM. In addition to exhibiting an accelerated growth rate, radioresistant GBM cells also have overexpression of the DNA synthesis-rate-limiting enzyme ribonucleotide reductase, and pro-cathepsin B. These newly identified genes should be concertedly studied to better understand their role in pediatric GBM recurrence and progression after radiation. It was observed that the changes in multiple biological pathways protected GBM cells against radiation and transformed them to a more malignant form. These changes emphasize the importance of developing a treatment regimen that consists of a multiple-agent cocktail that acts on multiple implicated pathways to effectively target irradiated pediatric GBM. An alternative to radiation or a novel therapy that targets differentially expressed genes, such as metalloproteases, growth factors, and oncogenes and aim to minimize oncogenic changes following radiation is necessary to improve recurrent GBM survival.
Author List
Alhajala HS, Nguyen HS, Shabani S, Best B, Kaushal M, Al-Gizawiy MM, Erin Ahn EY, Knipstein JA, Mirza S, Schmainda KM, Chitambar CR, Doan NBAuthors
Mona Al-Gizawiy PhD Assistant Professor in the Biophysics department at Medical College of WisconsinKathleen M. Schmainda PhD Professor in the Biophysics department at Medical College of Wisconsin