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Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity

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 deh...

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Main Authors: Schniewind, Iñaki (Author) , Hadiwikarta, Wahyu Wijaya (Author) , Grajek, Julia (Author) , Poleszczuk, Jan (Author) , Richter, Susan (Author) , Peitzsch, Mirko (Author) , Müller, Johannes (Author) , Klusa, Daria (Author) , Beyreuther, Elke (Author) , Löck, Steffen (Author) , Lühr, Armin (Author) , Frosch, Susanne (Author) , Groeben, Christer (Author) , Sommer, Ulrich (Author) , Krause, Mechthild (Author) , Dubrovska, Anna (Author) , Neubeck, Cläre von (Author) , Kurth, Ina (Author) , Peitzsch, Claudia (Author)
Format: Article (Journal)
Language:English
Published: February 22, 2022
In: Cell reports
Year: 2022, Volume: 38, Issue: 8, Pages: 1-22
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110422
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.celrep.2022.110422
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S2211124722001462
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Author Notes:Iñaki Schniewind, Wahyu Wijaya Hadiwikarta, Julia Grajek, Jan Poleszczuk, Susan Richter, Mirko Peitzsch, Johannes Müller, Daria Klusa, Elke Beyreuther, Steffen Löck, Armin Lühr, Susanne Frosch, Christer Groeben, Ulrich Sommer, Mechthild Krause, Anna Dubrovska, Cläre von Neubeck, Ina Kurth, and Claudia Peitzsch
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Summary: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.
Item Description:Gesehen am 13.05.2022
Physical Description:Online Resource
ISSN:2211-1247
DOI:10.1016/j.celrep.2022.110422

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