Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells

N. J. Sullivan, A. K. Sasser, A. E. Axel, F. Vesuna, V. Raman, N. Ramirez, T. M. Oberyszyn, B. M. Hall

Research output: Contribution to journalArticlepeer-review

Abstract

Breast tumor interleukin-6 (IL-6) levels increase with tumor grade, and elevated serum IL-6 correlates with poor breast cancer patient survival. Epithelial-mesenchymal transition (EMT) phenotypes such as impaired E-cadherin expression or aberrant Vimentin induction are associated with enhanced metastasis and unfavorable clinical outcome in breast cancer. Despite this fact, few tumor microenvironment-derived extracellular signaling factors capable of provoking such a phenotypic transition have been identified. In this study, we showed that IL-6 promoted E-cadherin repression among a panel of estrogen receptor-α-positive human breast cancer cells. Furthermore, ectopic stable IL-6 expressing MCF-7 breast adenocarcinoma cells (MCF-7 IL6) exhibited an EMT phenotype characterized by impaired E-cadherin expression and induction of Vimentin, N-cadherin, Snail and Twist. MCF-7 IL6 cells formed xenograft tumors that displayed loss of E-cadherin, robust Vimentin induction, increased proliferative indices, advanced tumor grade and undifferentiated histology. Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.

Original languageEnglish (US)
Pages (from-to)2940-2947
Number of pages8
JournalOncogene
Volume28
Issue number33
DOIs
StatePublished - Aug 20 2009

Keywords

  • Breast cancer
  • Epithelial-mesenchymal transition
  • Interleukin-6
  • Metastasis
  • Tumor microenvironment

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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