Breast cancer stem cells expressing different stem cell markers exhibit distinct biological characteristics.

Abstract

Identification and isolation of breast cancer stem cells (CSCs) based on CD44/CD24 expression and/or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1). However, the differences among the CD44+/CD24−/low cells, ALDH1+ cells and the overlap between the sub-populations have not been frequently investigated. Thus, it is imperative to improve the understanding of breast CSC with different stem markers. CD44+/CD24−/low, ALDH1+ and ALDH1+CD44+/CD24−/low cell populations were isolated from fresh breast cancer tissues and analyzed by flow cytometry and immunofluorescence. Mammosphere formation, cell proliferation assay and Transwell experiments, were used to analyze self-renewal, proliferation and invasion, respectively, for each sub-population. Finally, in vivo experimentation in mice was performed to evaluate the tumorigenic abilities of the sub-populations. The sub-populations of CD44+/CD24−/low, ALDH1+ and ALDH1+CD44+/CD24−/low in human breast cancer cells, represented the 7.2, 4.6 and 1.5% of the total tumor cell population, respectively. ALDH1+CD44+/CD24−/low cells had the strongest ability of self-renewal, invasion, proliferation and tumorigenicity compared with the other sub-populations (P<0.05). In conclusion, different phenotypes of CD44+/CD24−/low, ALDH1+ and ALDH1+CD44+/CD24−/low were isolated and demonstrated that breast CSCs are heterogeneous, and they exhibit distinct biological characteristics. As ALDH1+CD44+/CD24−/low cells demonstrated the strongest stem-like properties, it may be a useful specific stem cell marker. The utilization of more reliable biomarkers to distinguish the breast CSC pool will be important for the development of specific target therapies for breast cancer.