Iron inhibits glioblastoma cell migration and polarization.

Autor: Shenoy G; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Kheirabadi S; Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA., Ataie Z; Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA., Sahu AP; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Palsa K; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Wade Q; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Khunsriraksakul C; Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA., Khristov V; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Slagle-Webb B; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA., Lathia JD; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Wang HG; Department of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania, USA., Sheikhi A; Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA.; Department of Biomedical Engineering, The Pennsylvania State University, University Park, Pennsylvania, USA., Connor JR; Department of Neurosurgery, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2023 Dec; Vol. 37 (12), pp. e23307.
DOI: 10.1096/fj.202202157RR
Abstrakt: Glioblastoma is one of the deadliest malignancies facing modern oncology today. The ability of glioblastoma cells to diffusely spread into neighboring healthy brain makes complete surgical resection nearly impossible and contributes to the recurrent disease faced by most patients. Although research into the impact of iron on glioblastoma has addressed proliferation, there has been little investigation into how cellular iron impacts the ability of glioblastoma cells to migrate-a key question, especially in the context of the diffuse spread observed in these tumors. Herein, we show that increasing cellular iron content results in decreased migratory capacity of human glioblastoma cells. The decrease in migratory capacity was accompanied by a decrease in cellular polarization in the direction of movement. Expression of CDC42, a Rho GTPase that is essential for both cellular migration and establishment of polarity in the direction of cell movement, was reduced upon iron treatment. We then analyzed a single-cell RNA-seq dataset of human glioblastoma samples and found that cells at the tumor periphery had a gene signature that is consistent with having lower levels of cellular iron. Altogether, our results suggest that cellular iron content is impacting glioblastoma cell migratory capacity and that cells with higher iron levels exhibit reduced motility.
(© 2023 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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