Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity
Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved..
Proton radiotherapy has been implemented into the standard-of-care for cancer patients within recent years. However, experimental studies investigating cellular and molecular mechanisms are lacking, and prognostic biomarkers are needed. Cancer stem cell (CSC)-related biomarkers, such as aldehyde dehydrogenase (ALDH), are known to influence cellular radiosensitivity through inactivation of reactive oxygen species, DNA damage repair, and cell death. In a previous study, we found that ionizing radiation itself enriches for ALDH-positive CSCs. In this study, we analyze CSC marker dynamics in prostate cancer, head and neck cancer, and glioblastoma cells upon proton beam irradiation. We find that proton irradiation has a higher potential to target CSCs through induction of complex DNA damages, lower rates of cellular senescence, and minor alteration in histone methylation pattern compared with conventional photon irradiation. Mathematical modeling indicates differences in plasticity rates among ALDH-positive CSCs and ALDH-negative cancer cells between the two irradiation types.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
Cell reports - 38(2022), 8 vom: 22. Feb., Seite 110422 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Schniewind, Iñaki [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 16.03.2022 Date Revised 16.03.2022 published: Print Citation Status MEDLINE |
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| doi: |
10.1016/j.celrep.2022.110422 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Proton radiotherapy has been implemented into the standard-of-care for cancer patients within recent years. However, experimental studies investigating cellular and molecular mechanisms are lacking, and prognostic biomarkers are needed. Cancer stem cell (CSC)-related biomarkers, such as aldehyde dehydrogenase (ALDH), are known to influence cellular radiosensitivity through inactivation of reactive oxygen species, DNA damage repair, and cell death. In a previous study, we found that ionizing radiation itself enriches for ALDH-positive CSCs. In this study, we analyze CSC marker dynamics in prostate cancer, head and neck cancer, and glioblastoma cells upon proton beam irradiation. We find that proton irradiation has a higher potential to target CSCs through induction of complex DNA damages, lower rates of cellular senescence, and minor alteration in histone methylation pattern compared with conventional photon irradiation. Mathematical modeling indicates differences in plasticity rates among ALDH-positive CSCs and ALDH-negative cancer cells between the two irradiation types | ||
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| 650 | 4 | |a epigenetics | |
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| 650 | 4 | |a head and neck squamous cell carcinomas | |
| 650 | 4 | |a prostate cancer | |
| 650 | 4 | |a proton irradiation | |
| 650 | 4 | |a radiobiology | |
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| 700 | 1 | |a Hadiwikarta, Wahyu Wijaya |e verfasserin |4 aut | |
| 700 | 1 | |a Grajek, Julia |e verfasserin |4 aut | |
| 700 | 1 | |a Poleszczuk, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Richter, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Peitzsch, Mirko |e verfasserin |4 aut | |
| 700 | 1 | |a Müller, Johannes |e verfasserin |4 aut | |
| 700 | 1 | |a Klusa, Daria |e verfasserin |4 aut | |
| 700 | 1 | |a Beyreuther, Elke |e verfasserin |4 aut | |
| 700 | 1 | |a Löck, Steffen |e verfasserin |4 aut | |
| 700 | 1 | |a Lühr, Armin |e verfasserin |4 aut | |
| 700 | 1 | |a Frosch, Susanne |e verfasserin |4 aut | |
| 700 | 1 | |a Groeben, Christer |e verfasserin |4 aut | |
| 700 | 1 | |a Sommer, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Krause, Mechthild |e verfasserin |4 aut | |
| 700 | 1 | |a Dubrovska, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a von Neubeck, Cläre |e verfasserin |4 aut | |
| 700 | 1 | |a Kurth, Ina |e verfasserin |4 aut | |
| 700 | 1 | |a Peitzsch, Claudia |e verfasserin |4 aut | |
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