Gene analysis and dynamics of tumor stem cells in human glioblastoma cells after radiation

Abstract

Glioblastoma is the most malignant central nervous system tumor. Patients with glioblastoma are treated with a combination of surgery, radiotherapy and chemotherapy; however, this effect is not satisfactory with regard to the prognosis. It is reported that the tumor stem cells affect recurrence, and radio- and chemotherapy resistance of the tumor, and that these cells play an important role in tumorigenesis and tumor progression. Using human glioblastoma cell lines (T98G and A172), irradiated (0, 30, 60 Gy) glioblastoma cells were prepared under the same conditions as clinical therapy. We analyzed cell proliferation rate, side population analysis by fluorescence-activated cell sorting and isolation of CD133⁺ cells, and performed genetic analysis (human stem cells) on these cells. We also investigated the difference in gene expression in the cells after radiation. The stem cell-related genes were highly expressed in the CD133⁺ cells compared with the CD133⁻ cells, suggesting that the cancer stem cells may be located in these CD133⁺ cells. In the T98G cell line, the cell proliferation rate of 30-Gy irradiated cells was higher than those of non-irradiated cells and 60-Gy irradiated cells. Stem cell-related genes were highly expressed in 30-Gy irradiated CD133⁺ T98G cells. In conclusion, we suggest that CD133⁺ cells may strongly affect tumor proliferation and the resistance against radiation therapy.

Temozolomide Resistance in Glioblastoma Cell Lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 Expression

“…In this context, we studied CD133+ population in our cell lines before and after TMZ treatment. CD133 expression has been associated with drug resistance in SK-N-SH [ 51 ] and A172 cell lines [ 52 ]. Our results showed a significant increase in the percentage of CD133+ cells after the first TMZ cycle in A172 and LN229 cell lines.…”

The role of micro-RNA in the regulation of signal pathways in gliomas

“…Высокая экспрессия miR-34a в клетках глиобластомы после облучения в дозе 60 Gy снижает экспрессию р53; таким образом, регуляция экспрессии miR-34a может индуцировать апоптоз даже в клетках глиобластомы, которые приобрели лучевую резистентность [106]. Несколько микро-РНК семейства let-7 были гиперэкспрессированы после облучения клеток глиобластомы линии M059K (let-7 способствует подавлению пролиферации клеток глиом), но гипоэкспрессированы в случае других клеток глиобластомы линии M059J.…”

Potential Applications of Imaging and Image-Guided Radiotherapy for Brain Metastases and Glioblastoma to Improve Patient Quality of Life

“…Recent studies in molecular biology have demonstrated the existence of cancer stem cells (CSCs) in GBM responsible for treatment failure. Despite high doses of radiation of 30–60 Gy in a single fraction, these CSCs continued to proliferate in cell cultures following radiation ( 5 ). The radio-resistance of GBM cells suggests that radiation dose escalation alone is not feasible to control tumor growth in the clinical setting because of the excessive neurotoxicity associated with such a high dose.…”