Study of radiosensitivity in cancer stem-like cells from glioblastoma cell line

Radiotherapy is one of the conventional treatments for solid tumors. Investigation of tumor radioresistance is important for future tumor radiotherapy. Biological bases on the resistance of tumor cells have not been fully understood. Recently several studies demonstrated that there is a small fraction in solid tumor which is highly resistant to ionizing radiation and that the radioresistant tumor cells often express some stem cell markers. This small population of cells is characteristic of stem cells and called cancer stem cell. It is highly resistant to ionizing radiation and it is suggested that resistance of cancers to both radiation and chemotherapeutic agents can be attributed to the features of the cancer stem cells. Therefore the clarification of cancer stem cells might solve the resistance of cancer to ionizing radiation. The purpose of this study is the analysis of cancer stem-like cells derived from established glioblastoma cell line and radiosensitivity in cancer stem-like cells using X-rays and heavy ion beam provided from HIMAC (heavy ion medical accelerator in Chiba) in NIRS (National Institute of Radiological Sciences). In the present study, we show that a human glioblastoma cell line A172 transiently becomes to cancer stem cell-like when cultured with non-serum media which is supplemented with several growth factors. A172 cells cultured with non-serum media supplemented with several growth factors showed the morphological change and formation of neurospheres, the characteristic of cultured neural stem cells. The treated cell population was significantly resistant to X-rays and heavy ion particles (carbon) compared with the A172 cells cultured with the normal media. Phosphorylation of histone gamma H2Ax by irradiation was induced in both forms, however, recovered earlier in the stem cell-like population than in the parental cells. As a conclusion, our result is consistent with the hypothesis that stemness of A172 glioblastoma cells contribute to radioresistance by the efficient repair activity on DNA double-strand breaks.14th ICR