Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone

Velidi H. Rao, Rakesh K Singh, Julia A. Bridged, James R. Neff, G. Bradley Schaefer, Duane C. Delimont, Christopher M. Dunn, Warren G. Sanger, Bruce A. Buehler, Raymond Sawaya, Garth L. Nicolson, Jasti S. Rao

Research output: Contribution to journalArticle

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Abstract

Matrix metalloproteinases (MMPs) play an important regulatory role in tissue morphogenesis, cell differentiation, tumor invasion and metastasis. Several authors have reported a direct correlation between the production of 72 kDa (MMP-2) and 92 kDa (MMP-9) type IV collagenases/gelatinases and the metastatic potential of cancer cells. Recently, we have identified the expression of both MMP-2 and MMP-9 in primary cultures of human giant cell tumor (GCT) of bone in vitro, and in tissue extracts in vivo. Interestingly, MMP-9 is not secreted by late-passaged GCT cells. It is possible that the production of MMP-9 is regulated by certain factor(s) secreted by the multinucleated giant cells in the primary culture. In order to test this hypothesis, the effect of primary-culture-conditioned medium on the expression of MMP-9 by late-passaged mononuclear stromal cells was examined. Adding conditioned medium from the primary GCT culture to the late-passaged stromal cells induced MMP-9, as evidenced by the presence of lytic bands at M(r) 92,000 and 72,000 on a gelatin zymogram. These enzyme activities were inhibited by EDTA, a well-known inhibitor of the MMPs. We confirmed these results by Western blotting using specific antibodies and RT-PCR for MMP-2 and MMP-9. Immunofluorescence studies with specific antibodies to MMP-9 further confirmed its expression by the passaged stromal cells cultured in the primary-culture-conditioned medium. The data indicate that MMP-2 and MMP-9 are produced by the mononuclear stromal cells when cultured in GCT primary-culture-conditioned medium. This suggests that multinucleated giant cells in primary cultures secrete a factor(s) that stimulates stromal cells to produce MMP-9, which, in turn, may contribute to the aggressive behavior of GCT.

Original languageEnglish (US)
Pages (from-to)400-409
Number of pages10
JournalClinical and Experimental Metastasis
Volume15
Issue number4
DOIs
StatePublished - Jul 22 1997

Fingerprint

Giant Cell Tumor of Bone
Matrix Metalloproteinase 9
Stromal Cells
Giant Cell Tumors
Matrix Metalloproteinase 2
Conditioned Culture Medium
Giant Cells
Gelatinases
Tissue Extracts
Matrix Metalloproteinase Inhibitors
Antibodies
Gelatin
Matrix Metalloproteinases
Morphogenesis
Edetic Acid
Fluorescent Antibody Technique
Cell Differentiation
Neoplasms
Cell Culture Techniques
Western Blotting

Keywords

  • Cytokines
  • Giant cell tumor
  • Metalloproteinases
  • Stromal cells

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone. / Rao, Velidi H.; Singh, Rakesh K; Bridged, Julia A.; Neff, James R.; Schaefer, G. Bradley; Delimont, Duane C.; Dunn, Christopher M.; Sanger, Warren G.; Buehler, Bruce A.; Sawaya, Raymond; Nicolson, Garth L.; Rao, Jasti S.

In: Clinical and Experimental Metastasis, Vol. 15, No. 4, 22.07.1997, p. 400-409.

Research output: Contribution to journalArticle

Rao, VH, Singh, RK, Bridged, JA, Neff, JR, Schaefer, GB, Delimont, DC, Dunn, CM, Sanger, WG, Buehler, BA, Sawaya, R, Nicolson, GL & Rao, JS 1997, 'Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone', Clinical and Experimental Metastasis, vol. 15, no. 4, pp. 400-409. https://doi.org/10.1023/A:1018450204980
Rao, Velidi H. ; Singh, Rakesh K ; Bridged, Julia A. ; Neff, James R. ; Schaefer, G. Bradley ; Delimont, Duane C. ; Dunn, Christopher M. ; Sanger, Warren G. ; Buehler, Bruce A. ; Sawaya, Raymond ; Nicolson, Garth L. ; Rao, Jasti S. / Regulation of MMP-9 (92 kDa type IV collagenase/gelatinase B) expression in stromal cells of human giant cell tumor of bone. In: Clinical and Experimental Metastasis. 1997 ; Vol. 15, No. 4. pp. 400-409.
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AU - Singh, Rakesh K

AU - Bridged, Julia A.

AU - Neff, James R.

AU - Schaefer, G. Bradley

AU - Delimont, Duane C.

AU - Dunn, Christopher M.

AU - Sanger, Warren G.

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AU - Nicolson, Garth L.

AU - Rao, Jasti S.

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