Document Detail

S100A4 regulates membrane induced activation of matrix metalloproteinase-2 in osteosarcoma cells.
MedLine Citation:
PMID:  14713104     Owner:  NLM     Status:  MEDLINE    
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-kappaB 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.
Berit Mathisen; Rune I Lindstad; Janne Hansen; Sara Ann El-Gewely; Gunhild M Maelandsmo; Eivind Hovig; Oystein Fodstad; Thrina Loennechen; Jan-Olof Winberg
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Clinical & experimental metastasis     Volume:  20     ISSN:  0262-0898     ISO Abbreviation:  Clin. Exp. Metastasis     Publication Date:  2003  
Date Detail:
Created Date:  2004-01-09     Completed Date:  2004-01-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8409970     Medline TA:  Clin Exp Metastasis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  701-11     Citation Subset:  IM    
Department of Biochemistry, Institute of Medical Biology, University of Tromsø, Tromsø, Norway.
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MeSH Terms
Bone Neoplasms / enzymology*
Calcium-Binding Proteins / pharmacology*
Cell Membrane / metabolism
Culture Media, Conditioned
Enzyme Activation
Matrix Metalloproteinase 2 / biosynthesis*
Osteosarcoma / enzymology*
S100 Proteins / pharmacology*
Tissue Inhibitor of Metalloproteinases / metabolism
Tumor Cells, Cultured
Reg. No./Substance:
0/Calcium-Binding Proteins; 0/Culture Media, Conditioned; 0/S100 Proteins; 0/Tissue Inhibitor of Metalloproteinases; 142662-27-9/S100A4 protein, human; EC Metalloproteinase 2

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