Tumour-initiating capacity is independent of epithelial–mesenchymal transition status in breast cancer cell lines

Abstract

Background:Epithelial–mesenchymal transition (EMT) and cancer stem cells (CSCs) are considered to be crucial for cancer biology. The purpose of this study was to determine whether EMT directly led to the acquisition of tumour-initiating capacity in breast cancer cell lines.Methods:Epithelial–mesenchymal transition was induced in five breast cancer cell lines and one normal breast cell line by EMT-related cytokine stimulation. Mesenchymal–epithelial transition (MET) was induced by stably overexpressing miR-200c in three mesenchymal-like breast cancer cell lines. Molecular expression and cell function analysis were performed to evaluate the effect of EMT or MET on tumour-initiating capacity and other biological characteristics.Results:The induction of EMT did not enhance tumour-initiating capacity but, instead, conferred a CD44+/CD24−/low phenotype as well as cell proliferation, migration, and resistance to doxorubicin and radiation on breast cancer cell lines. Furthermore, MET did not lead to inhibition or loss of the tumour-initiating capacity in mesenchymal-like breast cancer cell lines, but it markedly attenuated other malignant properties, including proliferation, invasion, and resistance to therapy.Conclusions:Epithelial–mesenchymal transition does not alter tumour-initiating capacity of breast cancer cells but some other biological characteristics. Therefore, EMT and tumour-initiating capacity may not be directly linked in breast cancer cell lines.

WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel

“…Since increased migration is considered a feature of EMT49, we determined if the loss of WT1 also affects the epithelial/mesenchymal balance of breast cancer cells and analysed the RNA levels of several EMT drivers ( SNAI1, SNAI2, ZEB1, ZEB2, TWIST1 ), epithelial markers ( CTNNA1, CTNNA2, CTNND1, CDH1, KRT18 ) and mesenchymal markers ( VIM, TNC, TGFB1, CDH2, MMP2, MMP9 ) through quantitative real-time PCR.…”

Epithelial–mesenchymal transition (EMT): A biological process in the development, stem cell differentiation, and tumorigenesis

“…Other studies of the relationship between the lineage transition and the tumor initiating capability indicated that induction of EMT in breast cancer cells is not associated with enhancing tumor‐initiating capacity, but instead, conferred a CD44 + /CD24 − phenotype and the malignant properties, including cell proliferation, migration, and resistance to chemotherapy and radiation. On the other hand, MET does not lead to inhibition or loss of the tumor‐initiating capacity, but markedly attenuated other malignant properties (Xie et al, ). Repression of the EMT inducer Prrx1 reverted the cells to the epithelial phenotype concomitant with the acquisition of the stem cell properties (Ocana et al, ).…”

The role of EMT and MET in cancer dissemination

“…Other studies indicate that the CSC or tumor initiating cell (TIC) populations exhibit a hybrid phenotype (55). Clearly, TIC capacity can exist within an epithelial phenotype (56, 57). Barriere and colleagues have suggested the following CSC markers to identify stem-like cells in the blood, regardless of whether they are epithelial or mesenchymal: Aldehyde dehydrogenase-1 (ALDH1), CD44, Gangliosides (GD2, GD3 and GD1a), and ATP-binding cassette transporters (ABC extrusion pump proteins) (58).…”