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Open AccessArticle

Radiosensitization and a Less Aggressive Phenotype of Human Malignant Glioma Cells Expressing Isocitrate Dehydrogenase 1 (IDH1) Mutant Protein: Dissecting the Mechanisms

1
Department of Radiotherapy, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06097 Halle (Saale), Germany
2
Department of Anatomy and Cell Biology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Große Steinstraße 52, 06108 Halle (Saale), Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(6), 889; https://doi.org/10.3390/cancers11060889
Received: 29 March 2019 / Revised: 9 June 2019 / Accepted: 11 June 2019 / Published: 25 June 2019
(This article belongs to the Special Issue Glioblastoma: State of the Art and Future Perspectives)
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Abstract

The presence of an isocitrate dehydrogenase 1 (IDH1) mutation is associated with a less aggressive phenotype, increased sensitivity to radiation, and increased overall survival in patients with diffuse glioma. Based on in vitro experimentations in malignant glioma cell lines, the consequences on cellular processes of IDH1R132H expression were analyzed. The results revealed that IDH1R132H expression enhanced the radiation induced accumulation of residual γH2AX foci and decreased the amount of glutathione (GSH) independent of the oxygen status. In addition, expression of the mutant IDH1 caused a significant increase of cell stiffness and induced an altered organization of the cytoskeleton, which has been shown to reinforce cell stiffness. Furthermore, IDH1R132H expression decreased the expression of vimentin, an important component of the cytoskeleton and regulator of the cell stiffness. The results emphasize the important role of mutant IDH1 in treatment of patients with diffuse gliomas especially in response to radiation. Hence, detection of the genetic status of IDH1 before therapy massively expands the utility of immunohistochemistry to accurately distinguish patients with a less aggressive and radiosensitive IDH1-mutant diffuse glioma suitable for radiotherapy from those with a more aggressive IDH1-wildtype diffuse glioma who might benefit from an individually intensified therapy comprising radiotherapy and alternative medical treatments. View Full-Text
Keywords: isocitrate dehydrogenase 1; IDH1; IDH1R132H; glioma; glioblastoma; cell stiffness; atomic force microscopy isocitrate dehydrogenase 1; IDH1; IDH1R132H; glioma; glioblastoma; cell stiffness; atomic force microscopy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Kessler, J.; Hohmann, T.; Güttler, A.; Petrenko, M.; Ostheimer, C.; Hohmann, U.; Bache, M.; Dehghani, F.; Vordermark, D. Radiosensitization and a Less Aggressive Phenotype of Human Malignant Glioma Cells Expressing Isocitrate Dehydrogenase 1 (IDH1) Mutant Protein: Dissecting the Mechanisms. Cancers 2019, 11, 889.

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