Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity

Birgitte Schmidt-Hansen, Dorte Örnås, Mariam Grigorian, Jörg Klingelhöfer, Eugene Tulchinsky, Eugene Lukanidin, Noona Ambartsumian

Research output: Contribution to journalArticlepeer-review

159 Citations (Scopus)

Abstract

S100A4(mts1) protein expression has been strongly associated with metastatic tumor progression. It has been suggested as a prognostic marker for a number of human cancers. It is proposed that extracellular S100A4 accelerates cancer progression by stimulating the motility of endothelial cells, thereby promoting angiogenesis. Here we show that in 3D culture mouse endothelial cells (SVEC 4-10) respond to recombinant S100A4 by stimulating invasive growth of capillary-like structures. The out-growth is not dependent on the stimulation of cell proliferation, but rather correlates with the transcriptional modulation of genes involved in the proteolytic degradation of extracellular matrix (ECM). Treatment of SVEC 4-10 with the S100A4 protein leads to the transcriptional activation of collagenase 3 (MMP-13) mRNA followed by subsequent release of the protein from the cells. β-Casein zymography demonstrates enhancement of proteolytic activity associated with MMP-13. This observation indicates that extracellular S100A4 stimulates the production of ECM degrading enzymes from endothelial cells, thereby stimulating the remodeling of ECM. This could explain the angiogenic and metastasis-stimulating activity of S100A4(mts1).

Original languageEnglish
Pages (from-to)5487-5495
Number of pages9
JournalOncogene
Volume23
Issue number32
DOIs
Publication statusPublished - Jul 15 2004
Externally publishedYes

Keywords

  • Angiogenesis
  • Extracellular activity
  • Metastasis-promoting
  • MMP-13 induction
  • S100A4

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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