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Quantitative MRI Evaluation of Ferritin Overexpression in Non-Small-Cell Lung Cancer.
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- معلومة اضافية
- المصدر:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
- بيانات النشر:
Original Publication: Basel, Switzerland : MDPI, [2000-
- الموضوع:
- نبذة مختصرة :
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 2 * MR mapping effectively detected FtH expression in our in vivo model. These results demonstrate that T 2 * 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 2 * mapping for potential use in patients to interrogate iron metabolic alterations and predict clinical outcomes.
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- Grant Information:
P01CA244091 United States NH NIH HHS; P01CA217797 United States NH NIH HHS; R21CA270742 United States NH NIH HHS; R50CA243693 United States NH NIH HHS; P30 CA008748 United States CA NCI NIH HHS; T32 CA078586 United States CA NCI NIH HHS; P30 CA086862 United States NH NIH HHS; R21CA256301 United States NH NIH HHS; T32CA078586 United States NH NIH HHS
- Contributed Indexing:
Keywords: MRI; T2*; electron paramagnetic resonance spectroscopy; ferritin; non-small-cell lung cancer
- الرقم المعرف:
9007-73-2 (Ferritins)
N12000U13O (Doxycycline)
E1UOL152H7 (Iron)
9013-31-4 (Apoferritins)
- الموضوع:
Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240523
- الموضوع:
20240523
- الرقم المعرف:
PMC10889593
- الرقم المعرف:
10.3390/ijms25042398
- الرقم المعرف:
38397073
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