Journal article
Iron promotes isocitrate dehydrogenase mutant glioma cell motility
Free radical biology & medicine, Vol.226, pp.109-116
01/2025
DOI: 10.1016/j.freeradbiomed.2024.11.032
PMID: 39551451
Abstract
Enriched iron metabolic features such as high transferrin receptor (TfR) expression and high iron content are commonly observed in aggressive gliomas and can be associated with poor clinical responses. However, the underlying question of how iron contributes to tumor aggression remains elusive. Gliomas harboring isocitrate dehydrogenase (IDH) mutations account for a high percentage (> 70 %) of recurrent tumors and cells with an acquired IDH mutation have been reported to have increased motility and invasion. This study aims to investigate how an acquired IDH mutation modulates iron metabolism and the implication(s) of iron on tumor cell growth. IDH mutant cells (U87R132H) grow significantly faster which is accompanied with increased TfR expression and iron uptake in vitro compared to wild-type U87 cells. This phenotype is retained in vivo. Biomechanically, U87R132H cells are significantly less stiff and supplementation with ferrous ammonium sulfate (Fe2+) augments membrane fluidity to drive U87R132H cells into a super motile state. These findings provide insight into how an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression.
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•Isocitrate dehydrogenase (IDH)-mutant glioma preferentially accumulate iron.•IDH-mutant glioma exhibit iron-dependent growth.•Iron modulates IDH-mutant glioma membrane fluidity to promote tumor cell motility.
Details
- Title: Subtitle
- Iron promotes isocitrate dehydrogenase mutant glioma cell motility
- Creators
- Stephenson Boakye Owusu - University of IowaEmily Russell - University of IowaAkalanka B. Ekanayake - University of IowaAlexei V. Tivanski - University of IowaMichael S. Petronek - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Free radical biology & medicine, Vol.226, pp.109-116
- DOI
- 10.1016/j.freeradbiomed.2024.11.032
- PMID
- 39551451
- NLM abbreviation
- Free Radic Biol Med
- ISSN
- 0891-5849
- eISSN
- 1873-4596
- Publisher
- Elsevier Inc
- Grant note
- Radiation Research Foundation: L998500-G Carver College of Medicine and the Holden Comprehensive Cancer Center, NIH: P30 CA086862
This work was supported by the Radiation Research Foundation (L998500-G) . Core facilities were supported in part by the Carver College of Medicine and the Holden Comprehensive Cancer Center, NIH P30 CA086862.
- Language
- English
- Date published
- 01/2025
- Academic Unit
- Iowa Neuroscience Institute; Radiation Oncology; Radiation Research Laboratory; Chemistry
- Record Identifier
- 9984749760202771
Metrics
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