@misc{oai:repo.qst.go.jp:00071170, author = {Sai, Sei and Wakai, Toshifumi and Vares, Guillaume and Kamada, Tadashi and 崔 星 and Guillaume Vares and 鎌田 正}, month = {Jun}, note = {Purpose: To investigate relationship between XRCC4 and cancer stem cell properties and further examine how XRCC4 involved in the radiosensitivity of putative human colon cancer stem cells after X-ray or carbon ion beam. Methods: Putative cancer stem cells sorted from HCT116-wild type (WT) and XRCC4 KO cells were treated with or without carbon ion or X-ray irradiation and then colony and spheroid formation assay, FACS analysis, gamma-H2AX foci assay, as well as in vivo tumor formation assay were performed. Results: FACS analysis showed that the percentage of CD44+ and ESA+ cells was significantly increased in XRCC4 KO cells (6.8%, and 7.2% vs 19.2% and 20%), whereas CD133+ was decreased (3.2% vs 1.6%) compared to HCT116-WT cells. The proportion of CD133+ and CD44+ cells was extremely increased in XRCC4 KO cells compared to HCT116-WT cells after X-ray irradiation. There was no change in proportion of ESA+ cells in HCT116-WT cells, but 10-fold enhancement of ESA+ cells was induced in HCT116-XRCC4 KO cells after X-ray irradiation. The number of colony and spheroid formed from CD133+, CD44+/ESA+ cells were significantly higher compared to that from CD133-, CD44-/ESA- cells in HCT116-XRCC4 KO cells, but extremely decreased compared to HCT116-WT cells. Analysis of cell survival fractions showed that CD133+, CD44+/ESA+ cells sorted from XRCC4 KO cells were predominantly radiosensitized compared to the that from HCT116-WT cells, especially after X-ray irradiation. A much more large number and large-sized gamma-H2AX foci were observed in CD44+/ESA+ cells sorted from XRCC4 KO cells compared to that from HCT116-WT cells, after 24 h carbon ion beam compared to X-ray irradiation. The in vivo tumorigenicity of XRCC4 KO cells is still retained and there are no differences between CD133+, CD44+/ESA+ cells and CD133-, CD44-/ESA- cells which sorted from XRCC4 KO cells. Conclusion: In conclusion, lack of XRCC4 significantly altered expression of cancer stem cell markers, radiosensitized cancer stem-like cells to both X-rays and carbon ion berams, suggesting that XRCC4 may play pivotal role in modulating cancer cell stemness., International Society for Stem Cell Research (ISSCR) 11 th Annual Meeting}, title = {The Role of XRCC4 in Human Colon Cancer Stem Cell Properties and Radiosensitivity}, year = {2013} }