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Open Access Highly Accessed Research article

Profiling of normal and malignant breast tissue show CD44high/CD24low phenotype as a predominant stem/progenitor marker when used in combination with Ep-CAM/CD49f markers

Hazem Ghebeh15, Ghida Majed Sleiman1, Pulicat S Manogaran1, Amer Al-Mazrou1, Eman Barhoush1, Falah H Al-Mohanna2, Asma Tulbah3, Khalid Al-Faqeeh4 and Chaker N Adra167*

Author Affiliations

1 Stem Cell & Tissue Re-engineering Program, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

2 Stem Cell & Tissue Re-engineering Program, Departments of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

3 Stem Cell & Tissue Re-engineering Program, Departments of Pathology, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

4 Stem Cell & Tissue Re-engineering Program, Department of Surgery, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia

5 College of Medicine, Al-Faisal University, Riyadh, Saudi Arabia

6 Transplantation Research Center (TRC), Brigham & Women's Hospital and Children’s Hospital Boston, Harvard Medical School, Boston,MA, USA

7 Stem Cell & Tissue Re-engineering Program, Research Centre, King Faisal Specialist Hospital and Research Centre, PO Box 3354, Riyadh, (MBC 03), 11211, Kingdom of Saudi Arabia

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BMC Cancer 2013, 13:289  doi:10.1186/1471-2407-13-289

Published: 14 June 2013

Abstract

Background

Accumulating evidence supports cancer to initiate and develop from a small population of stem-like cells termed as cancer stem cells (CSC). The exact phenotype of CSC and their counterparts in normal mammary gland is not well characterized. In this study our aim was to evaluate the phenotype and function of stem/progenitor cells in normal mammary epithelial cell populations and their malignant counterparts.

Methods

Freshly isolated cells from both normal and malignant human breasts were sorted using 13 widely used stem/progenitor cell markers individually or in combination by multi-parametric (up to 9 colors) cell sorting. The sorted populations were functionally evaluated by their ability to form colonies and mammospheres, in vitro.

Results

We have compared, for the first time, the stem/progenitor markers of normal and malignant breasts side-by-side. Amongst all markers tested, we found CD44high/CD24low cell surface marker combination to be the most efficient at selecting normal epithelial progenitors. Further fractionation of CD44high/CD24low positive cells showed that this phenotype selects for luminal progenitors within Ep-CAMhigh/CD49f + cells, and enriches for basal progenitors within Ep-CAM-/low/CD49f + cells. On the other hand, primary breast cancer samples, which were mainly luminal Ep-CAMhigh, had CD44high/CD24low cells among both CD49fneg and CD49f + cancer cell fractions. However, functionally, CSC were predominantly CD49f + proposing the use of CD44high/CD24low in combination with Ep-CAM/CD49f cell surface markers to further enrich for CSC.

Conclusion

Our study clearly demonstrates that both normal and malignant breast cells with the CD44high/CD24low phenotype have the highest stem/progenitor cell ability when used in combination with Ep-CAM/CD49f reference markers. We believe that this extensive characterization study will help in understanding breast cancer carcinogenesis, heterogeneity and drug resistance.

Keywords:
Normal breast; Stem cells; Breast cancer; Flow cytometry; CD10; ALDH; CD44high/CD24low; MUC-1; Mammary gland