Feng, H.* ; Schorpp, K.K. ; Jin, J.* ; Yozwiak, C.E.* ; Hoffstrom, B.G.* ; Decker, A.M.* ; Rajbhandari, P.* ; Stokes, M.E.* ; Bender, H.G.* ; Csuka, J.M.* ; Upadhyayula, P.S.* ; Canoll, P.* ; Uchida, K.* ; Soni, R.K.* ; Hadian, K. ; Stockwell, B.R.*
Transferrin receptor is a specific ferroptosis marker.
Cell Rep. 30, 3411-3423.e7 (2020)
Ferroptosis is a type of regulated cell death driven by the iron-dependent accumulation of oxidized polyunsaturated fatty acid-containing phospholipids. There is no reliable way to selectively stain ferroptotic cells in tissue sections to characterize the extent of ferroptosis in animal models or patient samples. We address this gap by immunizing mice with membranes from lymphoma cells treated with the ferroptosis inducer piperazine erastin and screening similar to 4,750 of the resulting monoclonal antibodies generated for their ability to selectively detect cells undergoing ferroptosis. We find that one antibody, 3F3 ferroptotic membrane antibody (3F3-FMA), is effective as a selective ferroptosis-staining reagent. The antigen of 3F3-FMA is identified as the human transferrin receptor 1 protein (TfR1). We validate this finding with several additional anti-TfR1 antibodies and compare them to other potential ferroptosis-detecting reagents. We find that anti-TfR1 and anti-malondialdehyde adduct antibodies are effective at staining ferroptotic tumor cells in multiple cell culture and tissue contexts.
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Publication type
Article: Journal article
Document type
Scientific Article
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Editors
Keywords
Biomarker ; Cancer ; Cell Death ; Ferroptosis ; Ferroptosis Marker ; Ferroptosis-specific Antibody ; Iron ; Ros ; Tissue Staining ; Transferrin Receptor; Dependent Iron Uptake; Cell-death; Endothelial-cells; Cancer-cells; Identification; Probe; Sensitivity; Metabolism; Oxidation; Biology
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Language
english
Publication Year
2020
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2020
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
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Volume: 30,
Issue: 10,
Pages: 3411-3423.e7
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Cell Press
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50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
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Reviewing status
Peer reviewed
POF-Topic(s)
30203 - Molecular Targets and Therapies
Research field(s)
Enabling and Novel Technologies
PSP Element(s)
G-505293-001
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Erfassungsdatum
2020-04-17