Abstract

Purpose: Iron acquisition is key to maintaining cell survival and function. Cancer cells in general are considered to have an insatiable iron need. Iron delivery via the transferrin/transferrin receptor pathway has been the canonical iron uptake mechanism. Recently, however, our laboratory and others have explored the ability of ferritin, particularly the H-subunit, to deliver iron to a variety of cell types. Here, we investigate whether Glioblastoma (GBM) initiating cells (GICs), a small population of stem-like cells, are known for their iron addiction and invasive nature acquire exogenous ferritin, as a source of iron. We further assess the functional impact of ferritin uptake on the invasion capacity of the GICs. Methods: To establish that H-ferritin can bind to human GBM, tissue-binding assays were performed on samples collected at the time of surgery. To interrogate the functional consequences of H-ferritin uptake, we utilized two patient-derived GIC lines. We further describe H-ferritin’s impact on GIC invasion capacity using a 3D invasion assay. Results: H-ferritin bound to human GBM tissue at the amount of binding was influenced by sex. GIC lines showed uptake of H-ferritin protein via transferrin receptor. FTH1 uptake correlated with a significant decrease in the invasion capacity of the cells. H-ferritin uptake was associated with a significant decrease in the invasion-related protein Rap1A. Conclusion: These findings indicate that extracellular H-ferritin participates in iron acquisition to GBMs and patient-derived GICs. The functional significance of the increased iron delivery by H-ferritin is a decreased invasion capacity of GICs potentially via reduction of Rap1A protein levels.

Original languageEnglish (US)
Pages (from-to)9691-9703
Number of pages13
JournalJournal of Cancer Research and Clinical Oncology
Volume149
Issue number12
DOIs
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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