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

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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 bothin vitro andin 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.

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Authors and Affiliations

  1. Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE, USA

    Velidi H. Rao, Julia A. Bridge, G. Bradley Schaefer & Bruce A. Buehler

  2. Departments of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, USA

    Velidi H. Rao & Julia A. Bridge

  3. Department of Orthopedic Surgery, University of Nebraska Medical Center, Omaha, NE, USA

    James R. Neff

  4. Department of Biochemistry, University of Nebraska Medical Center, Omaha, NE, USA

    Jamboor K. Vishwanatha

  5. Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Raphael E. Pollock

  6. Department of Tumor Biology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Garth L. Nicolson

  7. Department of Neurosurgery, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA

    Masaaki Yamamoto, Ziya L. Gokaslam, Raymond Sawaya & Jasti S. Rao

  8. Laboratory of Pathology, NCI, Bethesda, MD, USA

    William G. Stetler-Stevenson

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  1. Velidi H. Rao
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Rao, V.H., Bridge, J.A., Neff, J.R. et al. Expression of 72 kDa and 92 kDa type IV collagenases from human giant-cell tumor of bone. Clin Exp Metast 13, 420–426 (1995). https://doi.org/10.1007/BF00118181

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  • DOI: https://doi.org/10.1007/BF00118181

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