Dkk-1 secreted by mesenchymal stem cells inhibits growth of breast cancer cells via depression of Wnt signalling

Cancer Lett. 2008 Sep 28;269(1):67-77. doi: 10.1016/j.canlet.2008.04.032. Epub 2008 Jun 20.

Abstract

We determined the molecular mechanism of inhibitory effect of human mesenchymal stem cells (hMSCs) on the growth of human MCF-7 breast cancer cells. Our finding showed that beta-catenin was down-regulated in MCF-7 cells by conditioned media from Z3 hMSCs, and the expression level of dickkopf-1 (Dkk-1) was higher in Z3 cells than that in MCF-7 cells. Neutralization of Dkk-1 and small interference RNA targeting Dkk-1 mRNA in Z3 cells attenuated the inhibitory effect of Z3 cells on MCF-7 cells. Overexpression of Dkk-1 in Z3 cells enhanced the inhibition. Therefore, Dkk-1 secreted by Z3 cells involves the inhibition via the Wnt pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Breast Neoplasms / pathology
  • Breast Neoplasms / prevention & control*
  • Cell Proliferation
  • Cells, Cultured
  • Culture Media, Conditioned
  • Humans
  • Intercellular Signaling Peptides and Proteins / analysis
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / physiology*
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • Mice, SCID
  • Signal Transduction / physiology*
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / physiology*
  • beta Catenin / physiology

Substances

  • Culture Media, Conditioned
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Wnt Proteins
  • beta Catenin