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

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

Original Publication: Basel, Switzerland : MDPI, [2000-

Carcinoma, Non-Small-Cell Lung*/diagnostic imaging ; Carcinoma, Non-Small-Cell Lung*/genetics ; Lung Neoplasms*/diagnostic imaging; Humans ; Ferritins/genetics ; Ferritins/metabolism ; Doxycycline/pharmacology ; Iron/metabolism ; Apoferritins/genetics ; Apoferritins/metabolism ; Magnetic Resonance Imaging/methods

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.

Front Immunol. 2021 Apr 01;12:612144. (PMID: 33868231)
Nat Rev Cancer. 2013 May;13(5):342-55. (PMID: 23594855)
Cancer Lett. 2016 Oct 28;381(2):331-40. (PMID: 27523281)
Cancers (Basel). 2019 Jul 30;11(8):. (PMID: 31366108)
J Magn Reson Imaging. 2003 Jul;18(1):33-9. (PMID: 12815637)
Clin Cancer Res. 2024 Jan 17;30(2):283-293. (PMID: 37773633)
Radiographics. 2009 Sep-Oct;29(5):1433-49. (PMID: 19755604)
Sci Rep. 2020 Feb 21;10(1):3163. (PMID: 32081948)
Iowa Orthop J. 2022 Jun;42(1):255-262. (PMID: 35821920)
Acta Radiol. 2020 Dec;61(12):1724-1732. (PMID: 32366108)
Cytokine. 2002 Jul 7;19(1):21-6. (PMID: 12200109)
Sci Rep. 2019 Aug 5;9(1):11326. (PMID: 31383898)
Antioxidants (Basel). 2021 Sep 14;10(9):. (PMID: 34573089)
Sci Rep. 2021 Oct 21;11(1):20817. (PMID: 34675308)
Sci Rep. 2021 Mar 15;11(1):6047. (PMID: 33723286)
World J Gastroenterol. 2011 Jan 28;17(4):522-5. (PMID: 21274383)
Eur J Cancer. 1992;28(1):241. (PMID: 1567668)
Radiology. 1991 Jun;179(3):777-81. (PMID: 2027991)
Nature. 2014 May 1;509(7498):105-9. (PMID: 24695223)
Scand J Gastroenterol. 2015 Apr;50(4):429-38. (PMID: 25633726)
Redox Biol. 2013 Nov 26;2:22-7. (PMID: 24396727)
Biochim Biophys Acta. 1996 Jul 31;1275(3):161-203. (PMID: 8695634)
Magn Reson Med. 2005 Jul;54(1):28-33. (PMID: 15968677)
Med Sci Monit. 2007 Apr;13(4):CR195-200. (PMID: 17392651)
PLoS One. 2019 Jan 14;14(1):e0208610. (PMID: 30640897)
Dev Cell. 2019 Dec 2;51(5):575-586.e4. (PMID: 31735663)
Iowa Orthop J. 2023 Dec;43(2):60-69. (PMID: 38213860)
Antioxidants (Basel). 2023 Nov 15;12(11):. (PMID: 38001858)
Magn Reson Med. 2011 Jul;66(1):248-54. (PMID: 21695727)
NMR Biomed. 2021 Mar;34(3):e4454. (PMID: 33325086)
Cell Death Dis. 2018 Dec 5;9(12):1174. (PMID: 30518922)

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

Keywords: MRI; T2*; electron paramagnetic resonance spectroscopy; ferritin; non-small-cell lung cancer

9007-73-2 (Ferritins)
N12000U13O (Doxycycline)
E1UOL152H7 (Iron)
9013-31-4 (Apoferritins)

Date Created: 20240224 Date Completed: 20240226 Latest Revision: 20240523

20240523

PMC10889593

10.3390/ijms25042398

38397073