Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone

Velidi H. Rao, Julia A. Bridge, James R. Neff, G. Bradley Schaefer, Bruce A. Buehler, Jamboor K. Vishwanatha, Raphael E. Pollock, Garth L. Nicolson, Masaaki Yamamoto, Ziya L. Gokaslam, William G. Stetler-Stevenson, Raymond Sawaya, Jasti S. Rao

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Basement membrane forms widespread barriers to tumor invasion. It has been shown that tumor-secreted, basement membrane-degrading enzymes, namely metalloproteinases (MMPs) play an important role in tumor invasion and metastasis. In this study, we determined the enzymatic activity, content, and mRNA of both the 72 kDa (MMP-2) and 92 kDa (MMP-9) MMPs in primary cultures of human giant-cell tumor of bone (GCT)in vitro and in tissue extracts (in vivo). Gelatin zymography showed the presence of lytic bands at Mr 121000, 92000, and 72000, and these enzymatic activities were inhibited by EDTA, an inhibitor of MMPs. Western blots with antibodies specific for MMP-2 and MMP-9 confirmed the presence of MMP-2 and MMP-9 both in vitro and in vivo, but GCT cells at late passage showed only MMP-2. Northern blots using labeled cDNA probes specific for these molecules revealed the presence of 3.1 kb transcript for MMP-2 and a 2.9 kb transcript for MMP-9. Using specific antibodies to 72 kDa and 92 kDa type IV collagenases, we studied their cellular distribution by immunohistochemical means. Stronger immunoreactivity was found for 92 kDa type IV collagenase than 72 kDa type IV collagenase in the giant cells. It appears, therefore, that MMP-9 may play an important role in the malignant behavior of GCTs and suggests a potential therapeutic role for protease inhibitors in attempting to minimize the invasive behavior of GCTs.

Original languageEnglish (US)
Pages (from-to)420-426
Number of pages7
JournalClinical & Experimental Metastasis
Volume13
Issue number6
DOIs
StatePublished - Nov 1995

Keywords

  • invasion
  • metalloproteinases
  • metastasis
  • tissue inhibitors of metalloproteinases

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Rao, V. H., Bridge, J. A., Neff, J. R., Schaefer, G. B., Buehler, B. A., Vishwanatha, J. K., Pollock, R. E., Nicolson, G. L., Yamamoto, M., Gokaslam, Z. L., Stetler-Stevenson, W. G., Sawaya, R., & Rao, J. S. (1995). Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone. Clinical & Experimental Metastasis, 13(6), 420-426. https://doi.org/10.1007/BF00118181