1. Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity
- Author
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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
- Subjects
Male ,Cell Line, Tumor ,Radiation, Ionizing ,Cell Plasticity ,Medizin ,Carcinoma, Squamous Cell ,Neoplastic Stem Cells ,Humans ,Aldehyde Dehydrogenase ,Protons ,Radiation Tolerance ,General Biochemistry, Genetics and Molecular Biology - 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.
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