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Erschienen in: Journal of Neuro-Oncology 3/2018

21.03.2018 | Laboratory Investigation

ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation

verfasst von: Yi Chieh Lim, Hazel Quek, Carolin Offenhäuser, Shazrul Fazry, Andrew Boyd, Martin Lavin, Tara Roberts, Bryan Day

Erschienen in: Journal of Neuro-Oncology | Ausgabe 3/2018

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Abstract

Glioblastoma (GBM) is a highly fatal disease with a 5 year survival rate of less than 22%. One of the most effective treatment regimens to date is the use of radiotherapy which induces lethal DNA double-strand breaks to prevent tumour growth. However, recurrence occurs in the majority of patients and is in-part a result of robust radioresistance mechanisms. In this study, we demonstrate that the multifunctional cytokine, interleukin-6 (IL-6), confers a growth advantage in GBM cells but does not have the same effect on normal neural progenitor cells. Further analysis showed IL-6 can promote radioresistance in GBM cells when exposed to ionising radiation. Ablation of the Ataxia-telangiectasia mutated serine/threonine kinase that is recruited and activated by DNA double-strand breaks reverses the effect of radioresistance and re-sensitised GBM to DNA damage thus leading to increase cell death. Our finding suggests targeting the signaling cascade of DNA damage response is a potential therapeutic approach to circumvent IL-6 from promoting radioresistance in GBM.
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Metadaten
Titel
ATM inhibition prevents interleukin-6 from contributing to the proliferation of glioblastoma cells after ionizing radiation
verfasst von
Yi Chieh Lim
Hazel Quek
Carolin Offenhäuser
Shazrul Fazry
Andrew Boyd
Martin Lavin
Tara Roberts
Bryan Day
Publikationsdatum
21.03.2018
Verlag
Springer US
Erschienen in
Journal of Neuro-Oncology / Ausgabe 3/2018
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-018-2838-0

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