Tumor radioresistance caused by radiation-induced changes of stem-like cell content and sub-lethal damage repair capability.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
20 01 2022
Historique:
received: 08 11 2021
accepted: 07 01 2022
entrez: 21 1 2022
pubmed: 22 1 2022
medline: 9 3 2022
Statut: epublish

Résumé

Cancer 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.

Identifiants

pubmed: 35058559
doi: 10.1038/s41598-022-05172-4
pii: 10.1038/s41598-022-05172-4
pmc: PMC8776741
doi:

Substances chimiques

Aldehyde Dehydrogenase EC 1.2.1.3

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1056

Subventions

Organisme : Japan Society for the Promotion of Science
ID : 20K16814
Organisme : Japan Society for the Promotion of Science
ID : 19K17215
Organisme : Japan Society for the Promotion of Science
ID : 19K08141

Informations de copyright

© 2022. The Author(s).

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Auteurs

Roman Fukui (R)

Department of Radiation Sciences, Graduate School of Health Science, Hirosaki Univesity, Hirosaki, Aomori, 036-8564, Japan.

Ryo Saga (R)

Department of Radiation Sciences, Graduate School of Health Science, Hirosaki Univesity, Hirosaki, Aomori, 036-8564, Japan. sagar@hirosaki-u.ac.jp.

Yusuke Matsuya (Y)

Nuclear Science and Engineering Center, Research Group for Radiation Transport Analysis, Japan Atomic Energy Agency (JAEA), Tokai, Ibaraki, 319-1195, Japan.

Kazuo Tomita (K)

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, 890-8544, Japan.

Yoshikazu Kuwahara (Y)

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, 890-8544, Japan.
Department of Radiation Biology and Medicine, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai, Miyagi, 983-8536, Japan.

Kentaro Ohuchi (K)

Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hok-Kaido, Tobetsu-cho, Ishikari-gun, Hokkaido, 061-0293, Japan.

Tomoaki Sato (T)

Department of Applied Pharmacology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Kagoshima, 890-8544, Japan.

Kazuhiko Okumura (K)

Department of Oral and Maxillofacial Surgery, School of Dentistry, Health Sciences University of Hok-Kaido, Tobetsu-cho, Ishikari-gun, Hokkaido, 061-0293, Japan.

Hiroyuki Date (H)

Faculty of Health Sciences, Hokkaido University, Sapporo, Hokkaido, 060-0812, Japan.

Manabu Fukumoto (M)

Pathology Informatics Team, RIKEN Center for Advanced Intelligence Project, Chuo-ku, Tokyo, 103-0027, Japan.

Yoichiro Hosokawa (Y)

Department of Radiation Sciences, Graduate School of Health Science, Hirosaki Univesity, Hirosaki, Aomori, 036-8564, Japan.

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