Cellular plasticity upon proton irradiation determines tumor cell radiosensitivity

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

Abstract

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.

Details

Original languageEnglish
Article number110422
Number of pages22
JournalCell reports
Volume38
Issue number8
Publication statusPublished - 22 Feb 2022
Peer-reviewedYes

External IDs

unpaywall 10.1016/j.celrep.2022.110422
Scopus 85124819689
WOS 000761232200009
Mendeley 545c22df-7bf7-3822-80f1-398da143fbdd

Keywords

Sustainable Development Goals

Keywords

  • cancer stem cells, cellular plasticity, epigenetics, glioblastoma, head and neck squamous cell carcinomas, prostate cancer, proton irradiation, radiobiology