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

Abstract

In radiotherapy, cancer stem cells (CSCs) are well recognized as one of the radioresistant cell types. Even in a small subpopulation, CSCs may have an influence on tumor control probability, represented by cell killing after irradiation. However, the relationship between the percentage content of CSCs and the cell survival dose–response curve has not yet been quantitatively clarified. In this study, we developed a cell-killing model for two cell populations (CSCs and progeny cells) to predict the surviving fractions, and compared it with the conventional linear–quadratic (LQ) model. Three prostate cancer cell lines (DU145, PC3 and LNCaP) were exposed to X-rays at doses ranging from 0 to 10 Gy. After the irradiation, we performed clonogenic survival assays to generate the cell survival curves, and carried out flow-cytometric analyses to estimate the percentage content of CSCs for each cell line. The cell survival curves for DU145 cells and PC3 cells seemed not to follow the conventional LQ model in the high dose range (>8 Gy). However, the outputs of the developed model agreed better with the experimental cell survival curves than those of the LQ model. The percentage content of CSCs predicted by the developed model was almost coincident with the measured percentage content for both DU145 cells and PC3 cells. The experiments and model analyses indicate that a small subpopulation of radioresistant CSCs has lower radiosensitivity in the high-dose range, which may lessen the clinical outcome for patients with prostate cancer after high-dose radiation therapy.

Physicochemical damage and early‐stage biological response to X‐ray radiation studied in prostate cancer cells by Raman spectroscopy

“…However, in this case, the predicted X‐ray doses significantly diverge from linearity. It is a consequence of an increasing radioresistance with an X‐ray dose, which has been shown to be typical for prostate cancer cells [34]. Indeed, regressions presented in Figure 3 show more quadratic pattern than those shown in Figure 2.…”

CSC Radioresistance: A Therapeutic Challenge to Improve Radiotherapy Effectiveness in Cancer

“…Using a xenograft model, our previous research work has shown that higher irradiation doses (6 Gy) are associated with tumor growth delay, probably due to CSC apoptotic death [ 96 ]. Saga [ 175 ] has suggested that in order to avoid recurrence or metastasis in prostate cancer the administration of higher doses would be necessary to eliminate the radioresistant CSCs. In addition to the cytotoxic effects, radiation plays a role in immune modulation in the tumor and TME.…”

Influence of adjuvant radiotherapy on circulating epithelial tumor cells and circulating cancer stem cells in primary non-metastatic breast cancer

“…By means of maintrac®, a non-dissipative method avoiding cell loss [20] , trajectories of circulating epithelial tumor cell (CETC) counts can be used as a marker for therapy response in the adjuvant situation allowing for continuous monitoring during treatment [21] . Monitoring the number of circulating tumor cells is superior to conventional imaging as a method for evaluating the response to different therapies, but has not yet been applied to assess the outcome of radiotherapy, especially in early breast cancer [ 18 , [22] , [23] , [24] , [25] , [26] , [27] , [28] ].…”