Clinical & Experimental Metastasis

, Volume 20, Issue 8, pp 701–711 | Cite as

S100A4 regulates membrane induced activation of matrix metalloproteinase-2 in osteosarcoma cells

  • Berit Mathisen
  • Rune I. Lindstad
  • Janne Hansen
  • Sara Ann El-Gewely
  • Gunhild M. Maelandsmo
  • Eivind Hovig
  • Øystein Fodstad
  • Thrina Loennechen
  • Jan-Olof WinbergEmail author


To study the role of the metastasis associated protein S100A4, an osteosarcoma cell line (OHS) with a high level of this protein was transfected with a vector containing a ribozyme that degrades S100A4 mRNA and, as controls, OHS cells were transfected with the vector alone. We have followed up our previous investigation (Bjørnland et al. 1999) by a detailed investigation of these cell lines' synthesis of MMP and TIMP proteins at different cell densities. It is shown that the cell lines with a low S100A4 level produced a reduced amount of immunoreactive MMP-2 at cellular subconfluence, while at confluence there was no difference compared to the control cells. The cell lines with a reduced S100A4 level produced less of the activated form of MMP-2 (62-kDa) and less TIMP-1 than the corresponding control cells, independent of cell density. Isolated cell membranes from cell lines with a reduced S100A4 level contained less MT1-MMP, MMP-2 and TIMP-2 compared to the control cells. Activation of exogenously added proMMP-2 was less effective with the former membrane preparations. It appeared that the mechanism behind the S100A4 dependent activation of proMMP-2 varied with cell density, as SN50, a peptide inhibitor of NF-κB nuclear translocation reduced the activation of MMP-2 at low cell density, but had no effect at high cell density. Thus, one of the mechanisms by which S100A4 may exert its effect on metastasis of some tumors is by regulating the MMP-2 activity.

inhibitors of matrix metalloproteinases matrix metalloproteinases metastasis NF-κB S100A4 


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Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Berit Mathisen
    • 1
  • Rune I. Lindstad
    • 1
  • Janne Hansen
    • 2
  • Sara Ann El-Gewely
    • 2
  • Gunhild M. Maelandsmo
    • 3
  • Eivind Hovig
    • 3
  • Øystein Fodstad
    • 3
  • Thrina Loennechen
    • 2
  • Jan-Olof Winberg
    • 1
    Email author
  1. 1.Department of Biochemistry, Institute of Medical BiologyUniversity of TromsøTromsøNorway
  2. 2.Department of Tumor BiologyThe Norwegian Radium HospitalOsloNorway
  3. 3.Department of Tumor BiologyThe Norwegian Radium HospitalOsloNorway

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