Adipose tissue-derived mesenchymal stem cells cultured at high density express IFN-β and suppress the growth of MCF-7 human breast cancer cells

Cancer Lett. 2014 Oct 1;352(2):220-7. doi: 10.1016/j.canlet.2014.06.018. Epub 2014 Jul 10.

Abstract

Although it has been reported that mesenchymal stem cells (MSCs) suppress tumor growth in vitro and in vivo, little is known about the underlying molecular mechanisms. We found that type I interferon is expressed in adipose tissue-derived stem cells (ASCs) cultured at high density, and ASCs and their conditioned medium (ASC-CM) suppress the growth of MCF-7 cells in vitro. Growth inhibition was amplified by glucose deprivation that resulted from high density culture of ASCs after 3days. The cytotoxic effect of the ASC-CM obtained from high density culture of ASCs was neutralized by anti-IFN-β antibody. STAT1 was phosphorylated in MCF-7 cells treated with ASC-CM, and JAK1/JAK2 inhibitor treatment decreased STAT1 phosphorylation. The cytotoxic effect of ASC-CM was reduced especially by JAK1 inhibitors in MCF-7 cells. Our findings suggest that ASCs cultured at high density express type I interferons, which suppresses tumor growth via STAT1 activation resulting from IFN-β secretion in MCF-7 breast cancer cells.

Keywords: Adipose tissue-derived stem cells; Growth suppression; High density culture; IFN-β; MCF-7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology
  • Adipose Tissue / metabolism*
  • Adult
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Count
  • Cell Proliferation* / drug effects
  • Coculture Techniques
  • Culture Media, Conditioned / metabolism
  • Female
  • Glucose / deficiency
  • Humans
  • Interferon-beta / metabolism*
  • Janus Kinase 1 / antagonists & inhibitors
  • Janus Kinase 1 / metabolism
  • Janus Kinase 2 / antagonists & inhibitors
  • Janus Kinase 2 / metabolism
  • MCF-7 Cells
  • Mesenchymal Stem Cells / metabolism*
  • Paracrine Communication* / drug effects
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction
  • Time Factors
  • Young Adult

Substances

  • Culture Media, Conditioned
  • Protein Kinase Inhibitors
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • Interferon-beta
  • JAK1 protein, human
  • JAK2 protein, human
  • Janus Kinase 1
  • Janus Kinase 2
  • Glucose