Sarmiento-Castro, Aida, Caamano-Gutierrez, Eva ORCID: 0000-0001-7737-5941, Sims, Andrew H, Hull, Nathan J, James, Mark I, Santiago-Gomez, Angelica, Eyre, Rachel, Clark, Christopher, Brown, Martha E, Brooks, Michael D et al (show 4 more authors)
(2020)
Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH<SUP>+</SUP> Breast Cancer Stem Cells.
STEM CELL REPORTS, 15 (2).
pp. 307-316.
Text
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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<sup>+</sup> cells) are enriched following AE treatment. Here, we show that the interleukin-1β (IL-1β) signaling pathway is activated in ALDH<sup>+</sup> cells, and data from single cells reveals that AE treatment selects for IL-1 receptor (IL1R1)-expressing ALDH<sup>+</sup> 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<sup>+</sup> 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<sup>+</sup>IL1R1<sup>+</sup> cells merits testing as a strategy to combat AE resistance in patients with residual disease.
Item Type: | Article |
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Uncontrolled Keywords: | Cell Line, Tumor, Humans, Breast Neoplasms, Neoplasm Metastasis, Estrogen Antagonists, Receptors, Interleukin-1, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Female, Neoplastic Stem Cells, Single-Cell Analysis, Transcriptome, Aldehyde Dehydrogenase 1 Family |
Depositing User: | Symplectic Admin |
Date Deposited: | 25 Sep 2020 08:01 |
Last Modified: | 12 Oct 2023 03:47 |
DOI: | 10.1016/j.stemcr.2020.06.020 |
Open Access URL: | https://doi.org/10.1016/j.stemcr.2020.06.020 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3102497 |