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Breast cancer stem cell markers CD44, CD24 and ALDH1: expression distribution within intrinsic molecular subtype
  1. Sara Ricardo1,2,3,
  2. André Filipe Vieira1,2,
  3. Renê Gerhard1,
  4. Dina Leitão1,4,
  5. Regina Pinto1,
  6. Jorge F Cameselle-Teijeiro5,
  7. Fernanda Milanezi1,
  8. Fernando Schmitt1,4,
  9. Joana Paredes1,4
  1. 1IPATIMUP—Institute of Molecular Pathology and Immunology of Porto University, Porto, Portugal
  2. 2ICBAS—Abel Salazar Biomedical Science Institute, Porto, Portugal
  3. 3Vale Polytechnic Health Institute of the North, Vale do Sousa Higher School of Health, Department of Anatomical Pathology Cytology and Tanatology, Gandra, Portugal
  4. 4Medical Faculty of Porto University, Porto, Portugal
  5. 5Complexo Hospitalar Universitario de Vigo (CHUVI), Vigo, Spain
  1. Correspondence to Joana Paredes, IPATIMUP, Rua Dr Roberto Frias s/n, 4200-465 Porto, Portugal; jparedes{at}ipatimup.pt

Abstract

Background and Aim The study of CD44/CD24 and ALDH1 expression is the most accurate method to identify cancer stem cells (CSC) from breast cancer populations. However, the overlap between CD44+CD24−/low and ALDH1high CSC phenotypes in breast cancer seems to be very small, as well as their distribution among intrinsic breast cancer subtypes. Due to this discrepancy, it is imperative to improve the understanding of breast CSC marker distribution.

Methods 466 invasive breast carcinomas and eight breast cancer cell lines were analysed for the expression of CD44, CD24 and ALDH1, to evaluate their distribution among the distinct molecular subtypes.

Results Basal-like tumours (76.5%) contained the higher percentage of cells with the CSC phenotype CD44+CD24−/low (p<0.0001). From ALDH1-positive cases, 39.4% were also basal-like tumours (p<0.0001). The analysis of breast cancer cell lines indicated that luminal cell lines are mainly enriched in a CD44−/lowCD24+ cell population, basal/mesenchymal breast cancer cell lines are enriched in the CD44+CD24−/low phenotype, whereas the remaining basal/epithelial cell lines are mainly positive for both markers. ALDH1 activity was mainly found in HER-OE and basal/epithelial breast cancer cell.

Conclusions CD44+CD24−/low and ALDH1+ phenotypes seem to identify CSC with distinct levels of differentiation. It seems that the paramount method and biomarkers that identify breast CSC within the distinct molecular subtypes need to be better explored, because it is pivotal to translate the CSC concept to clinical practice. In the future, the recognition of reliable markers to distinguish the CSC pool in each molecular subtype will be decisive for the development of specific target therapies.

  • ALDH1
  • breast cancer
  • breast cancer stem cells
  • CD24
  • CD44
  • molecular subtypes
  • tumour markers

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Footnotes

  • Funding The work presented was mainly supported by a scientific project funded by Fundação Calouste Gulbenkian and by research grants funded by the Portuguese Science and Technology Foundation (FCT): a PhD research grant for AFV (SFRH/BD/41363/2007) and the Programa Ciência 2007 for JP.

  • Competing interests None to declare.

  • Ethics approval This study was conducted under the national regulative law for the handling of biological specimens from tumour banks, being the samples exclusively available for research purposes in retrospective studies.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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