Glioma stem cells promote radioresistance by preferential activation of the DNA damage response

Shideng Bao, et al., Nature, 444:756 (2006)

Speaker : 張明俐                                          Time : 2007.03.28 13:10 ~ 14:00

Commentator : 黃溫雅老師                         Place : Room 601

Abstract:

Glioblastoma is the most lethal forms of gliomas with a median survival of 10-12 month.  Even though gliomas have a dismal prognosis; radiation is the most successful nonsurgical treatment for them. However, glioblastoma is well known for its recurrence from radiotherapy. Therefore, understanding this character might be useful for cancer therapy. From the brain tumor examined, recent study found that distinct subpopulations of cells expressed brain stem cell marker CD133⁽¹⁾.  The unique self-renewal and long-lived property of stem cells, which tumor cells are similar with, suggest that cancers might arise from them. In this study, the authors show that glioblastoma cells expressing CD133 are resistant to ionizing radiation because they are more efficient in inducing the repair of damaged DNA than the tumor cells do. These results show that radiation treatment fails in the long run because it cannot kill the subpopulation of CD133⁺ tumor-initiating cells. The glioblastoma cells grown in vitro or as grafts in mice which treated with ionzing-radiation produced an increased fraction of CD133⁺ cells in the residual tumor population compared with that in unirradiated tumors. These cells retained the ability to reinitiate heterogenous tumors when transplanted into other mice, demonstrating the retention of stem-cell ability. Although both CD133⁺ and CD133^- cells sustained a similar amount of DNA damage, activation of DNA-repair responses was greater in CD133⁺ cells. Moreover, the authors found that CD133⁺ cells could be rendered less resistant to radiation if Chk1 and Chk2, which control pauses in the cell cycle to allow DNA repair to take place, were inhibited. From this exciting research, there are a lot of interesting questions to be answered, such as where is the niche for glioma stem-like cells in vivo or does the niche provides an additional protection which is independent of DNA damage response.

Reference:

1. Singh, S.K. et al. Nature 432:396, (2004)