Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha.

  • Authors:
    • V H Rao
    • R K Singh
    • D C Delimont
    • R H Finnell
    • J A Bridge
    • J R Neff
    • B P Garvin
    • D L Pickering
    • W G Sanger
    • B A Buehler
    • G B Schaefer
  • View Affiliations

  • Published online on: February 1, 1999     https://doi.org/10.3892/ijo.14.2.291
  • Pages: 291-591
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

We determined whether certain factor(s) secreted by multinucleated giant cells, which is of monocyte/macrophage lineage in giant cell tumor of bone (GCT), regulate the induction of matrix metalloproteinase (MMP)-9 expression in mononucleated stromal cells. Our data derived using enzyme linked immunosorbant assays (ELISAs) suggest that the GCT cells in primary culture produce both MMP-9 and tumor necrosis factor-alpha (TNF-alpha). Further, the MMP-9 expression in GCT primary cultures was partially abrogated by neutralizing antibody to TNF-alpha, suggesting that TNF-alpha secretion by the multinucleated giant cells may be one of the factors responsible for the production of MMP-9 by the stromal cells in vivo. In order to confirm this we examined the role of TNF-alpha on the induction of MMP-9 expression in bone GCT stromal cells. These cells express MMP-2, but not MMP-9. However, treatment of these cells with TNF-alpha induced the expression of MMP-9 in a concentration-dependent manner. Kinetic experiments revealed that the secretion of MMP-9 peaked 12 h post TNF-alpha stimulation. Immunofluorescence studies confirmed the expression of MMP-9 after stimulation of GCT stromal cells with TNF-alpha. Further, TNF-alpha-induced MMP-9 expression was completely blocked with neutralizing antibody to TNF-alpha, thereby demonstrating the specificity. In addition, the induction of MMP-9 expression by TNF-alpha was completely abrogated in the presence of cycloheximide, a protein synthesis inhibitor, suggesting that de novo protein synthesis may be required. Nuclear run-on analysis demonstrated that treatment of GCT stromal cells significantly enhanced the MMP-9 gene transcription. Together, our data suggest that TNF-alpha secreted by the multinucleated giant cells up-regulates MMP-9 expression in GCT stromal cells by the induction of certain transcription factors, which in turn enhanced the rate of transcription of MMP-9 gene. These studies also suggest the existence of an essential cell-cell interaction in the regulation of MMP-9 expression in GCT.

Related Articles

Journal Cover

February 1999
Volume 14 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Rao, V., Singh, R., Delimont, D., Finnell, R., Bridge, J., Neff, J. ... Schaefer, G. (1999). Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha.. International Journal of Oncology, 14, 291-591. https://doi.org/10.3892/ijo.14.2.291
MLA
Rao, V., Singh, R., Delimont, D., Finnell, R., Bridge, J., Neff, J., Garvin, B., Pickering, D., Sanger, W., Buehler, B., Schaefer, G."Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha.". International Journal of Oncology 14.2 (1999): 291-591.
Chicago
Rao, V., Singh, R., Delimont, D., Finnell, R., Bridge, J., Neff, J., Garvin, B., Pickering, D., Sanger, W., Buehler, B., Schaefer, G."Transcriptional regulation of MMP-9 expression in stromal cells of human giant cell tumor of bone by tumor necrosis factor-alpha.". International Journal of Oncology 14, no. 2 (1999): 291-591. https://doi.org/10.3892/ijo.14.2.291