Cancer stem cells are prevalent in the basal-like 2 and mesenchymal triple-negative breast cancer subtypes in vitro

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Maxim Olsson¹  Toshima Z. Parris²  Peter Larsson²  Vasu R. Sah³  Junko Johansson³ 

[1] Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden;Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden;

关键词: tumor-initiating cells;    CD24;    CD44;    aldehyde dehydrogenase;    flow cytometry;   

DOI  :  10.3389/fcell.2023.1237673

 received in 2023-06-12, accepted in 2023-08-14,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Triple-negative breast cancer (TNBC) is an aggressive subtype with the most unfavorable clinical outcomes, in part due to tumor heterogeneity, treatment resistance, and tumor relapse. The TNBC subtypes [basal-like 1 (BL1), basal-like 2 (BL2), mesenchymal (M), and luminal androgen receptor (LAR)] are biologically and clinically distinct entities that respond differently to local and systemic therapies. Therefore, we need to have a better understanding of cancer stemness relating to drug-resistant populations in the TNBC subtypes.Methods: Breast cancer stem cell (BCSC) distribution was investigated using an integrated flow cytometry approach with the ALDEFLUOR™ assay (ALDH) and CD24/CD44 antibodies. In total, 27 commercially available cell lines derived from normal and malignant mammary tissue were characterized into differentiated tumor cells and/or BCSC subpopulations (ALDH−CD44+CD24-/low enriched mesenchymal-like BCSCs, ALDH+non-CD44+CD24−/low enriched epithelial-like BCSCs, and highly purified ALDH+CD44+CD24−/low BCSCs).Results: BCSCs were not only enriched in estrogen receptor (ER) negative (mean, 49.6% versus 6.9% in ER+) and TNBC cell lines (51.3% versus 2.1% in Luminal A), but certain BCSC subpopulations (e.g., enriched mesenchymal-like BCSCs) were also significantly more common in the M (64.0% versus 6.2% in BL1; 64.0% versus 0% in LAR) and BL2 (77.4% versus 6.2% in BL1; 77.4% versus 0% in LAR; 77.4% versus 10.4% in TNBC UNS) TNBC subtypes. In contrast, ALDH status alone was not indicative of ER status or BC subtype.Conclusion: Taken together, these findings demonstrate the enrichment of potentially treatment-resistant BCSC subpopulations in the M and BL2 triple-negative breast cancer subtypes.

【 授权许可】

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Copyright © 2023 Olsson, Larsson, Johansson, Sah and Parris.