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IDH1R132H mutation causes a less aggressive phenotype and radiosensitizes human malignant glioma cells independent of the oxygenation status
- Source :
- Radiotherapy and Oncology. 116:381-387
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- In malignant glioma the presence of the IDH1 mutation (IDH1(R132H)) is associated with better clinical outcome. However, it is unclear whether IDH1 mutation is associated with a less aggressive phenotype or directly linked to increased sensitivity to radiotherapy.We determined the influence of IDH1(R132H) mutant protein on proliferation and growth in 3D culture, migration, cell survival and radiosensitivity in vitro under normoxia (21% O2) and hypoxia (1% O2) in a panel of human malignant glioma cell lines (U-251MG, U-343MG, LN-229) with stable overexpression of wild-type (IDH1(wt)) and mutated IDH1 (IDH1(R132H)).Overexpression of IDH1(R132H) in glioma cells resulted in slightly decreased cell proliferation, considerably reduced cell migration and caused differences in growth properties in 3D spheroid cultures. Furthermore, IDH1(R132H)-positive cells consistently demonstrated an increased radiosensitivity in human malignant glioma cells U-251MG (DMF10: 1.52, p0.01 and 1.42, p0.01), U-343MG (DMF10: 1.78, p0.01 and 1.75, p0.01) and LN-229 (DMF10: 1.41, p0.05 and 1.68, p0.01) under normoxia and hypoxia, respectively.Our data indicate that IDH1(R132H) mutation causes both a less aggressive biological behavior and direct radiosensitization of human malignant glioma cells. Targeting IDH1 appears to be an attractive approach in combination with radiotherapy.
- Subjects :
- Radiation-Sensitizing Agents
IDH1
Cell Survival
Biology
medicine.disease_cause
Radiation Tolerance
Mutant protein
Glioma
medicine
Humans
Radiology, Nuclear Medicine and imaging
Radiosensitivity
Hypoxia
Cell Proliferation
Mutation
Cell growth
Cell migration
Hematology
medicine.disease
Phenotype
Isocitrate Dehydrogenase
Oncology
Cancer research
Subjects
Details
- ISSN :
- 01678140
- Volume :
- 116
- Database :
- OpenAIRE
- Journal :
- Radiotherapy and Oncology
- Accession number :
- edsair.doi.dedup.....75c6d82092df39082c2f8e5c62a49c57