Increased Expression of Interleukin-1 Receptor Characterizes Anti-estrogen-Resistant ALDH+ Breast Cancer Stem Cells

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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+ Breast Cancer Stem Cells. STEM CELL REPORTS, 15 (2). pp. 307-316.

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Official URL: http://dx.doi.org/10.1016/j.stemcr.2020.06.020

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-1β (IL-1β) 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.

Item Type:	Article
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:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3102497