Journal
CELL REPORTS
Volume 30, Issue 10, Pages 3411-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.02.049
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Funding
- NIH [P30 CA013696]
- National Cancer Institute [R35CA209896, P01CA087497]
- National Institute for Neurological Disorders and Stroke [1R61NS109407]
- Emerson Collective
- Columbia College Science Scholars program
- Arnold and Mabel Beckman Foundation's Beckman Scholar Award
- M.J. Murdock Charitable Trust
- [TL1 TR001875]
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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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