Regularities and Mechanisms of Radiation Effects on Cancer Stem Cells In Vitro and In Vivo

Abstract

Radioresistance of cancer stem cells (CSCs) is regarded as one of possible causes of cancer recurrence after radiotherapy. Since the regularities and mechanisms of radiation effects on this population of cells have not been studied enough, the aim of this work is to elucidate the changes of CSC number after ionizing radiation exposure of stable cultures of tumor cells in vitro and tumor tissue in vivo (in the course of radiation therapy of patients with cancer of the upper respiratory tract). CSCs were identified in cell lines B16, MCF-7, HeLa by the ability to efflux the fluorescent dye Hoechst 33342 (SP method) 48–72 h after irradiation at doses of 1–20 Gy and in biopsy material by immunophenotype CD44+CD24-/low before and 24 h after irradiation at the total focal dose of 10 Gy. The essential differences in the response of CSCs and the rest of cancer cells were found after exposure to the low-, but not high-LET (neutron) radiation. CSCs of all the three lines had a higher resistance to 60Co γ—radiation exposure than the rest of the cells. Fractionated γ-irradiation in vivo at the total dose of 10 Gy increased the relative amount of CSCs in most patients. The higher resistance of CSCs to low-LET radiation can be explained by a number of reasons, including low proliferative activity, low number of radiation-induced double-strand DNA breaks, high levels of radiation-induced expression of HSP70 and especially HSP27.