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    Increased expression of interleukin-1 receptor characterizes anti-estrogen-resistant ALDH(+) breast cancer stem cells

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    Authors
    Sarmiento-Castro, Aida
    Caamaño-Gutiérrez, E
    Sims, Andrew H
    Hull, N J
    James, M
    Santiago-Gómez, Angélica
    Eyre, Rachel
    Clark, Christopher
    Brown, M. E.
    Brooks, M. D.
    Wicha, M. S.
    Howell, Sacha J
    Clarke, Robert B
    Simões, Bruno M
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    Affiliation
    Manchester Breast Centre, Division of Cancer Sciences, University of Manchester, Manchester
    Issue Date
    2020
    
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    Abstract
    Estrogen-receptor-positive breast tumors are treated with anti-estrogen (AE) therapies but frequently develop resistance. Cancer stem cells (CSCs) with high aldehyde dehydrogenase activity (ALDH+ cells) are enriched following AE treatment. Here, we show that the interleukin-1? (IL-1?) signaling pathway is activated in ALDH+ cells, and data from single cells reveals that AE treatment selects for IL-1 receptor (IL1R1)-expressing ALDH+ cells. Importantly, CSC activity is reduced by an IL1R1 inhibitor in AE-resistant models. Moreover, IL1R1 expression is increased in the tumors of patients treated with AE therapy and predicts treatment failure. Single-cell gene expression analysis revealed that at least two subpopulations exist within the ALDH+ population, one proliferative and one quiescent. Following AE therapy the quiescent population is expanded, which suggests CSC dormancy as an adaptive strategy that facilitates treatment resistance. Targeting of ALDH+IL1R1+ cells merits testing as a strategy to combat AE resistance in patients with residual disease. Keywords: ALDH(+) cells; IL1R1; anti-estrogens; breast cancer stem cells; dormancy.
    Citation
    Sarmiento-Castro A, Caamano-Gutierrez E, Sims AH, Hull NJ, James MI, Santiago-Gomez A, et al. Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH(+) Breast Cancer Stem Cells. Stem Cell Reports. 2020;15(2):307-16.
    Journal
    Stem Cell Reports
    URI
    http://hdl.handle.net/10541/623198
    DOI
    10.1016/j.stemcr.2020.06.020
    PubMed ID
    32707076
    Additional Links
    https://dx.doi.org/10.1016/j.stemcr.2020.06.020
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.stemcr.2020.06.020
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