Analysis of the high-dose-range radioresistance of prostate cancer cells, including cancer stem cells, based on a stochastic model

Saga, Ryo*; Matsuya, Yusuke; Takahashi, Rei*; Hasegawa, Kazuki*; Date, Hiroyuki*; Hosokawa, Yoichiro*

Journal of Radiation Research, 60(3), p.298 - 307, 2019/05

https://doi.org/10.1093/jrr/rrz011

In radiotherapy, it is recognized that cancer stem cells (CSCs) in tumor tissue shows radio-resistance. However, the relationship between content percentage of the CSCs and dose-response curve on cell survival remain unclear. In this study, we developed a stochastic model considering progeny cells and stem cells, and investigated the impact of stem cells on radio-sensitivity. From the flow-cytometric analysis (cell experiments), the content percentage of stem cells was 3.2% or less which agreed well with the model estimation from the cell survival curve. Based on the verification, it is suggested that cell survival in high-dose range is largely affected by the CSCs. In addition, regarding the sub-population of stem cells, the present model well reproduces the dose response on lethal lesions to DNA comparing with the conventional LQ model. This outcome indicates that the stem cells must be considered for describing the dose-response curve in wide dose range.