Do Different Stemness Markers Identify Different Pools of Cancer Stem Cells in Malignancies: A Study on ER+ and ER-Breast Cancer Cell Lines

Abstract

In view of popularity of cancer stem cell (CSC) model all events in evolution of cancer are being explained in that context. Breast cancer is first solid tumor in which CSCs were identified. We aimed to compare stemness profile of two major subtypes [Estrogen receptor positive (ER⁺) and negative (ER⁻)] breast cancer using different sets of markers. Expression of CD44/CD24, CK/Vimentin, E-Cadherin/Fibronectin and percentage of side population (SP) was studied in ER⁺ (T47D) and ER⁻ (MDA-MB-231) cell lines by flow cytometry. Breast CSCs (BCSCs) were sorted using CD44⁺/CD24^−/low expression and SP analysis and cultured. BCSCs were then compared with Non-CSCs (NCSCs) for response to drugs (Paclitaxel and Cisplatin), Ki67 and ER expression. Results showed higher expression of stemness markers (CD44⁺/CD24^−/low, CK⁺/Vimentin⁺ and E-Cadherin⁻/Fibrinectin^F+) in MDA-MB-231 cells. Percentage SP representing BCSCs was found to be significantly more in later (3.20 ± 0.002 cf. T47D 1.25% ± 0.0007). BCSCs were found to be more resistant to drugs as compared to NCSCs in both cell lines. ER expression was weak in BCSCs sorted from T47D as compared to NCSCs. Ki67 was expressed in both BCSCs and NCSCs. Differences in expression of stemness markers help to explain aggressive behavior, higher recurrence rate and metastatic potential of MDA-MB-231 cells. However, no correlation amongst different markers used suggests that they may be identifying varied populations of cells in tumor hierarchy. A weak ER expression in BCSCs may be strategy used by BCSCs to escape effect of hormone therapy in ER⁺ breast cancers.

https://ift.tt/2D68l15