Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer

Mekhla Singhania; Amira Zaher; Casey F Pulliam; Khaliunaa Bayanbold; Charles C Searby; Joshua D Schoenfeld; Kranti A Mapuskar; Melissa A Fath; Bryan G Allen; Douglas R Spitz; Michael S Petronek

doi:10.3390/ijms25042398

Back

Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer

Journal article

Open access

Peer reviewed

Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer

Mekhla Singhania, Amira Zaher, Casey F Pulliam, Khaliunaa Bayanbold, Charles C Searby, Joshua D Schoenfeld, Kranti A Mapuskar, Melissa A Fath, Bryan G Allen, Douglas R Spitz, …

International journal of molecular sciences, Vol.25(4), 2398

02/18/2024

DOI: 10.3390/ijms25042398

PMCID: PMC10889593

PMID: 38397073

Files and links (1)

url

https://doi.org/10.3390/ijms25042398View

Published (Version of record) Open Access

Abstract

Cancer cells frequently present elevated intracellular iron levels, which are thought to facilitate an enhanced proliferative capacity. Targeting iron metabolism within cancer cells presents an avenue to enhance therapeutic responses, necessitating the use of non-invasive models to modulate iron manipulation to predict responses. Moreover, the ubiquitous nature of iron necessitates the development of unique, non-invasive markers of metabolic disruptions to develop more personalized approaches and enhance the clinical utility of these approaches. Ferritin, an iron storage enzyme that is often upregulated as a response to iron accumulation, plays a central role in iron metabolism and has been frequently associated with unfavorable clinical outcomes in cancer. Herein, we demonstrate the successful utility, validation, and functionality of a doxycycline-inducible ferritin heavy chain (FtH) overexpression model in H1299T non-small-cell lung cancer (NSCLC) cells. Treatment with doxycycline increased the protein expression of FtH with a corresponding decrease in labile iron in vitro and in vivo, as determined by calcein-AM staining and EPR, respectively. Moreover, a subsequent increase in TfR expression was observed. Furthermore, T * MR mapping effectively detected FtH expression in our in vivo model. These results demonstrate that T * relaxation times can be used to monitor changes in FtH expression in tumors with bidirectional correlations depending on the model system. Overall, this study describes the development of an FtH overexpression NSCLC model and its correlation with T * mapping for potential use in patients to interrogate iron metabolic alterations and predict clinical outcomes.

ferritin

MRI

electron paramagnetic resonance spectroscopy

non-small-cell lung cancer

Details

Title: Subtitle: Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer
Creators: Mekhla Singhania - University of Iowa
Amira Zaher - University of Iowa
Casey F Pulliam - University of Iowa
Khaliunaa Bayanbold - University of Iowa
Charles C Searby - University of Iowa
Joshua D Schoenfeld - Memorial Sloan Kettering Cancer Center
Kranti A Mapuskar - University of Iowa
Melissa A Fath - University of Iowa
Bryan G Allen - University of Iowa
Douglas R Spitz - University of Iowa
Michael S Petronek - University of Iowa
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.25(4), 2398
DOI: 10.3390/ijms25042398
PMID: 38397073
PMCID: PMC10889593
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Grant note: R21CA270742 / NIH HHS P30 CA086862 / NIH HHS T32CA078586 / NIH HHS P01CA244091 / NIH HHS P01CA217797 / NIH HHS R50CA243693 / NIH HHS R21CA256301 / NIH HHS
Language: English
Date published: 02/18/2024
Academic Unit: Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
Record Identifier: 9984560491002771

Metrics

10 Record Views

5 Times Cited - Web of Science