Author:
Fukui Roman,Saga Ryo,Matsuya Yusuke,Tomita Kazuo,Kuwahara Yoshikazu,Ohuchi Kentaro,Sato Tomoaki,Okumura Kazuhiko,Date Hiroyuki,Fukumoto Manabu,Hosokawa Yoichiro
Abstract
AbstractCancer stem-like cells (CSCs) within solid tumors exhibit radioresistance, leading to recurrence and distant metastasis after radiotherapy. To experimentally study the characteristics of CSCs, radioresistant cell lines were successfully established using fractionated X-ray irradiation. The fundamental characteristics of CSCs in vitro have been previously reported; however, the relationship between CSC and acquired radioresistance remains uncertain. To efficiently study this relationship, we performed both in vitro experiments and theoretical analysis using a cell-killing model. Four types of human oral squamous carcinoma cell lines, non-radioresistant cell lines (SAS and HSC2), and radioresistant cell lines (SAS-R and HSC2-R), were used to measure the surviving fraction after single-dose irradiation, split-dose irradiation, and multi-fractionated irradiation. The SAS-R and HSC2-R cell lines were more positive for one of the CSC marker aldehyde dehydrogenase activity than the corresponding non-radioresistant cell lines. The theoretical model analysis showed that changes in both the experimental-based ALDH (+) fractions and DNA repair efficiency of ALDH (−) fractions (i.e., sub-lethal damage repair) are required to reproduce the measured cell survival data of non-radioresistant and radioresistant cell lines. These results suggest that the enhanced cell recovery in SAS-R and HSC2-R is important when predicting tumor control probability in radiotherapy to require a long dose-delivery time; in other words, intensity-modulated radiation therapy is ideal. This work provides a precise understanding of the mechanism of radioresistance, which is induced after irradiation of cancer cells.
Funder
Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Reference59 articles.
1. Atun, R. et al. Expanding global access to radiotherapy. Lancet Oncol. 16, 1153–1186 (2015).
2. McGarry, C. K. et al. Temporal characterization and in vitro comparison of cell survival following the delivery of 3D conformal, intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Phys. Med. Biol. 56, 2445–2457 (2011).
3. Garibaldi, E., Gabriele, D., Maggio, A. & Delmastro, E. External beam radiotherapy with dose escalation in 1080 prostate cancer patients: Definitive outcome and dose impact. Panminerva Med. 58, 121–129 (2016).
4. Burman, C. et al. Planning, delivery, and quality assurance of intensity-modulated radiotherapy using dynamic multileaf collimator: A strategy for large-scale implementation for the treatment of carcinoma of the prostate. Int. J. Radiat. Oncol. Biol. Phys. 39, 863–873 (1997).
5. Robert, D., Timmerman, M. D., Forster, K. M. & Cho, L. C. Extracranial stereotactic radiation delivery. Semin. Radiat. Oncol. 15, 202–207 (2005).
Cited by
15 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献