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

Br J Cancer. 2014 May 13;110(10):2514-23. doi: 10.1038/bjc.2014.153. Epub 2014 Apr 22.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibiotics, Antineoplastic / pharmacology
  • Antigens, Neoplasm / analysis
  • Breast Neoplasms / pathology*
  • Cell Division
  • Cell Line, Tumor
  • Cell Movement
  • Cholera Toxin / pharmacology
  • Cytokines / pharmacology
  • Doxorubicin / pharmacology
  • Drug Resistance, Neoplasm
  • Epithelial-Mesenchymal Transition / drug effects
  • Epithelial-Mesenchymal Transition / physiology*
  • Female
  • Humans
  • Hyaluronan Receptors / analysis
  • Hydrocortisone / pharmacology
  • Immunophenotyping
  • Insulin / pharmacology
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • MicroRNAs / physiology
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / physiology*
  • Neoplastic Stem Cells / radiation effects
  • Radiation Tolerance

Substances

  • Antibiotics, Antineoplastic
  • Antigens, Neoplasm
  • CD44 protein, human
  • Cytokines
  • Hyaluronan Receptors
  • Insulin
  • MIRN200 microRNA, human
  • MicroRNAs
  • Doxorubicin
  • Cholera Toxin
  • Hydrocortisone