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 (U87) 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, U87cells are significantly less stiff and supplementation with ferrous ammonium sulfate (Fe) augments membrane fluidity to drive U87cells 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.
Overview
- The study investigates how an acquired IDH mutation modulates iron metabolism and its impact on tumor cell growth in gliomas. The study uses U87 cells, which harbor an acquired IDH mutation, and compares their growth and iron metabolism to wild-type U87 cells. The study finds that IDH mutant cells grow significantly faster and have increased TfR expression and iron uptake in vitro and in vivo. Additionally, the study finds that U87 cells are less stiff and supplementation with Fe augments membrane fluidity to drive U87 cells into a super motile state. The study aims to 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.
Comparative Analysis & Findings
- The study finds that IDH mutant cells grow significantly faster than wild-type U87 cells and have increased TfR expression and iron uptake in vitro and in vivo. Additionally, the study finds that U87 cells are less stiff and supplementation with Fe augments membrane fluidity to drive U87 cells into a super motile state. These findings suggest that an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression.
Implications and Future Directions
- The study provides 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. The study suggests that an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression. The study also identifies that U87 cells are less stiff and supplementation with Fe augments membrane fluidity to drive U87 cells into a super motile state. These findings suggest that an acquired IDH mutation may be able to modulate iron metabolism, allowing iron to serve as a biomechanical driver of tumor progression. Future research could explore the role of iron in the biomechanical properties of gliomas and the potential of targeting iron metabolism as a therapeutic strategy for gliomas.