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Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity

Authors :
Schniewind, I.
Hadiwikarta, W. W.
Grajek, J.
Poleszczuk, J.
Richter, S.
Peitzsch, M.
(0000-0003-1273-2412) Müller, J.
Klusa, D.
(0000-0002-0582-1444) Beyreuther, E.
(0000-0002-7017-3738) Löck, S.
Lühr, A.
Frosch, S.
Groeben, C.
Sommer, U.
(0000-0003-1776-9556) Krause, M.
(0000-0002-3375-1500) Dubrovska, A.
Neubeck, C.
Kurth, I.
Peitzsch, C.
Schniewind, I.
Hadiwikarta, W. W.
Grajek, J.
Poleszczuk, J.
Richter, S.
Peitzsch, M.
(0000-0003-1273-2412) Müller, J.
Klusa, D.
(0000-0002-0582-1444) Beyreuther, E.
(0000-0002-7017-3738) Löck, S.
Lühr, A.
Frosch, S.
Groeben, C.
Sommer, U.
(0000-0003-1776-9556) Krause, M.
(0000-0002-3375-1500) Dubrovska, A.
Neubeck, C.
Kurth, I.
Peitzsch, C.
Source :
Cell Reports 38(2022)8, 110422
Publication Year :
2022

Abstract

Novel particle therapy was implemented into standard-of-care for cancer patients during the last years. However, experimental studies investigating cellular and molecular mechanisms are lacking and prognostic biomarker are urgently needed. Cancer stem cell (CSC)-related biomarkers such as aldehyde dehydrogenase (ALDH) are known to cellular radiosensitivity by affecting defense against reactive oxygen species, DNA damage repair and cell survival. Within a previous study, we found that ionizing radiation itself enriches for ALDH-positive CSCs. Within the present study, we investigated CSC marker dynamics in prostate cancer, head and neck cancer and glioblastoma cells upon proton beam irradiation. We found that proton irradiation has an increased CSC targeting potential, reduced methylation of activating histone marks and a lower induction of cellular senescence compared to conventional photon irradiation. Interestingly, mathematical modeling indicated to differences in plasticity rates among ALDH-positive CSCs and ALDH-negative cancer cells between the two irradiation types.

Details

Database :
OAIster
Journal :
Cell Reports 38(2022)8, 110422
Notes :
application/pdf, English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1415627564
Document Type :
Electronic Resource