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Transferrin Receptor Is a Specific Ferroptosis Marker.

32160546
PMC7172030
Cell reports
March 10, 2020
Department of Biological Sciences, Columbia University, Northwest Corner Building, 12th Floor, MC 4846, 550 West 120(th) Street, New York, NY 10027, USA; Department of Chemistry, Columbia University, Northwest Corner Building, 12th Floor, MC 4846, 550 West 120(th) Street, New York, NY 10027, USA; Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical Center, New York, NY 10032, USA. Electronic address: bstockwell@columbia.edu.
R35 CA209896, P01 CA087497, TL1 TR001875, R61 NS109407, P30 CA013696
Feng H, Schorpp K, Jin J, Yozwiak CE, Hoffstrom BG, Decker AM, Rajbhandari P, Stokes ME, Bender HG, Csuka JM, Upadhyayula PS, Canoll P, Uchida K, Soni RK, Hadian K, Stockwell BR
Feng H, Schorpp K, Jin J, Yozwiak CE, Hoffstrom BG, Decker AM, Rajbhandari P, Stokes ME, Bender HG, Csuka JM, Upadhyayula PS, Canoll P, Uchida K, Soni RK, Hadian K, Stockwell BR. Transferrin Receptor Is a Specific Ferroptosis Marker. Cell reports 2020 Mar 10.

Abstract

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 ∼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.