دورية أكاديمية
أعرض في EDS

Homeostatic iron regulatory protein drives glioblastoma growth via tumor cell-intrinsic and sex-specific responses.

التفاصيل البيبلوغرافية
العنوان: Homeostatic iron regulatory protein drives glioblastoma growth via tumor cell-intrinsic and sex-specific responses.
المؤلفون: Troike KM; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Molecular Medicine, Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA., Wang SZ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Medical Scientist Training Program, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.; Department of Pathology, Case Western Reserve University, Cleveland, Ohio, USA., Silver DJ; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA., Lee J; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Mulkearns-Hubert EE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Hajdari N; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Ghosh PK; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Kay KE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Molecular Medicine, Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA., Beilis JL; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Mitchell SE; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Bishop CW; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA., Hong ES; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Medical Scientist Training Program, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Artomov M; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.; Department of Pediatrics, The Ohio State Wexner Medical Center, Columbus, Ohio, USA., Hubert CG; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.; Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio, USA., Rajappa P; Institute for Genomic Medicine, Nationwide Children's Hospital, Columbus, Ohio, USA.; Department of Neurological Surgery, The Ohio State Wexner Medical Center, Columbus, Ohio, USA., Connor JR; Department of Neurosurgery, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA., Fox PL; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA., Kristensen BW; Department of Clinical Medicine, Biotech Research and Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark., Lathia JD; Department of Cardiovascular and Metabolic Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.; Department of Molecular Medicine, Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.; Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio, USA.; Rose Ella Burkhardt Brain Tumor and Neuro-Oncology Center, Cleveland Clinic, Cleveland, Ohio, USA.
المصدر: Neuro-oncology advances [Neurooncol Adv] 2023 Nov 28; Vol. 6 (1), pp. vdad154. Date of Electronic Publication: 2023 Nov 28 (Print Publication: 2024).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 101755003 Publication Model: eCollection Cited Medium: Internet ISSN: 2632-2498 (Electronic) Linking ISSN: 26322498 NLM ISO Abbreviation: Neurooncol Adv Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Oxford] : Oxford University Press, [2019]-
مستخلص: Background: Glioblastoma (GBM) displays alterations in iron that drive proliferation and tumor growth. Iron regulation is complex and involves many regulatory mechanisms, including the homeostatic iron regulator ( HFE ) gene, which encodes the homeostatic iron regulatory protein. While HFE is upregulated in GBM and correlates with poor survival outcomes, the function of HFE in GBM remains unclear.
Methods: We interrogated the impact of cell-intrinsic Hfe expression on proliferation and survival of intracranially implanted animals through genetic gain- and loss-of-function approaches in syngeneic mouse glioma models, along with in vivo immune assessments. We also determined the expression of iron-associated genes and their relationship to survival in GBM using public data sets and used transcriptional profiling to identify differentially expressed pathways in control compared to Hfe -knockdown cells.
Results: Overexpression of Hfe accelerated GBM proliferation and reduced animal survival, whereas suppression of Hfe induced apoptotic cell death and extended survival, which was more pronounced in females and associated with attenuation of natural killer cells and CD8+ T cell activity. Analysis of iron gene signatures in Hfe -knockdown cells revealed alterations in the expression of several iron-associated genes, suggesting global disruption of intracellular iron homeostasis. Further analysis of differentially expressed pathways revealed oxidative stress as the top pathway upregulated following Hfe loss. Hfe knockdown indeed resulted in enhanced 55 Fe uptake and generation of reactive oxygen species.
Conclusions: These findings reveal an essential function for HFE in GBM cell growth and survival, as well as a sex-specific interaction with the immune response.
Competing Interests: None declared.
(© The Author(s) 2023. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
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معلومات مُعتمدة: P01 CA245705 United States CA NCI NIH HHS; T32 GM007250 United States GM NIGMS NIH HHS
فهرسة مساهمة: Keywords: HFE; glioblastoma; iron; reactive oxygen species; sex difference
تواريخ الأحداث: Date Created: 20240119 Latest Revision: 20240410
رمز التحديث: 20240410
مُعرف محوري في PubMed: PMC10794878
DOI: 10.1093/noajnl/vdad154
PMID: 38239626
قاعدة البيانات: MEDLINE
الوصف
تدمد:2632-2498
DOI:10.1093/noajnl/vdad154