Why are breast cancer stem cells resistant to radiation?
Final rept. 1 Mar 2011-28 Feb 2013
PITTSBURGH UNIV PA
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There are contradictory observations on radiosensitivity in cancer stem cells vs. non-stem cells. To resolve these contradictory observations, we employed breast cancer stem cell CSC-like MDA-MB231 and MDA-MB453 cells as well as their corresponding non-stem cells. CSC-like cells proliferate without differentiating and have characteristics of tumor-initiating cells. These cells were exposed to -rays 1.25-8.75Gy and survival curves were determined by colony formation. A final slope, D0, of the survival curve for each cell line was determined to measure radiosensitivity. The D0 of CSC-like and non-MDA-MB453 cells were 1.16 Gy and 1.55 Gy, respectively. Similar results were observed in MDA-MB231 cells. After determination of radiosensitivity, we investigated intrinsic cellular determinants which influence radiosensitivity. We further examined whether CSC-like cells are relatively radiosensitive owing to different intrinsic factors including cell cycle distribution, free-radical scavengers and DNA repair. We observed that even though cell cycle status and antioxidant content may contribute to differential radiosensitivity, differential DNA repair capacity may be a greater determinant. Unlike non-CSC cells, CSC-like cells have littleno sublethal damage repair and a low intracellular level of ATM. These results suggest that low DNA repair capacity is responsible for the high radiosensitivity of these CSC-like cells.
- Medicine and Medical Research