Effect of heavy ion beam irradiation on radioresistance and differentiation of cancer stem cells in neuronal tumors

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The purpose is to investigate the radiobiological effect of heavy ion (CI) beams on radioresistance and differentiation of human tumor cells, especially cancer stem cells. Human ependymoblastoma with wild-type p53 and glioblastoma with mutant-type p53 were transplanted into nude mice and irradiated with CI beams or 150-kV X-rays. Tumors were excised for cDNA microarray analysis 6- 48 hours or 6 weeks after 2-24 Gy irradiation. CD133, CD44, Nestin, p53, PTEN, Ki67, and GFAP expressions were evaluated immunohistochemically. In ependymoblastoma, p53 signaling and apoptosis-related pathways were suggested to be involved following irradiation. The tumors showed a significant decrease in growth fraction and a slight increase of the CD133-positive rate after high-dose irradiation. These results suggest that CD133-positive and Ki-67-negative cells may be resistant to both X-rays and CI beams.