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

Maxim Olsson; Peter Larsson; Junko Johansson; Vasu R Sah; Toshima Z Parris

doi:10.3389/fcell.2023.1237673

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

Front Cell Dev Biol. 2023 Sep 12:11:1237673. doi: 10.3389/fcell.2023.1237673. eCollection 2023.

Authors

Maxim Olsson¹, Peter Larsson^{2

3}, Junko Johansson^{3

4}, Vasu R Sah^{3

4}, Toshima Z Parris^{2

3}

Affiliations

¹ Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
² Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
³ Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Surgery, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Abstract

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.

Keywords: CD24; CD44; aldehyde dehydrogenase; flow cytometry; tumor-initiating cells.

Grants and funding

Funding was provided by King Gustav V Jubilee Clinic Research Foundation, Magnus Bergvall Research Foundation, Cancer och Allergifonden, Åke Wiberg Research Foundation, Serena Ehrenström Research Foundation, and Wilhelm och Martina Lundgren Research Foundation. Open access funding was provided by the University of Gothenburg.