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Gene analysis and dynamics of tumor stem cells in human glioblastoma cells after radiation
Authors:Akiko Sasaki  Takato Nakajo  Yuko Tsunoda  Gou Yamamoto  Yusuke Kobayashi  Mayumi Tsuji  Yuko Udaka  Tohru Mizutani  Katsuji Oguchi
Institution:1. Department of Pharmacology, School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawaku, Tokyo, 142-8666, Japan
2. Department of Neurosurgery School of Medicine, Showa University, Hatanodai 1-5-8, Shinagawaku, Tokyo, 142-8666, Japan
3. Breast Center, Kameda Medical Center, 929 Higashi-cho, Kamogawa City, Chiba, 296-8602, Japan
4. Department of Oral Pathology, School of Dentistry, Showa University, Hatanodai 1-5-8, Shinagawaku, Tokyo, 142-8666, Japan
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.
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