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Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo

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Abstract

The 72 kDa type IV collagenase (gelatinase), a matrix metalloproteinase (MMP-2), has been proposed to potentiate the invasion and metastasis of malignant tumors. To determine the potential role of the MMP-2 in human gliomas and normal brain tissue, we examined the relative amounts of protein, mRNA, and distribution. Using gelatin zymography, densitometry, and an enzyme-linked immunosorbent assay for the quantitative determination of the MMP-2, we found that the enzyme's activity was significantly elevated in malignant astrocytomas, especially in glioblastoma multiforme, compared to low-grade glioma and normal brain tissues. As determined by Northern blot analysis, the amount of MMP-2 mRNA transcript was higher in anaplastic astrocytomas and glioblastoma multiforme tumors than in normal brain tissues or low-grade gliomas, a finding that was consistent with the amounts of MMP-2 protein detected in these tissues. Immunohistochemical studies demonstrated that MMP-2 was localized in tumor cells and vasculature cells of malignant astrocytomas. Staining intensity was clearly lower in low-grade astrocytomas, and immunoreactivity was very low or undetectable in normal brain astrocytes. The results suggest that expression of the MMP-2 is dramatically upregulated in malignant gliomas, correlating with the malignant progression of human gliomas in vivo.

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Authors and Affiliations

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

    Reymond E. Sawaya, Masaaki Yamamoto, Ziya L. Gokaslan, Shang Wu Wang, Sanjeeva Mohanam, Ian E. McCutcheon & Jasti S. Rao

  2. Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX

    Gregory N. Fuller

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

    Garth L. Nicolson

  4. Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA

    William G. Stetler-Stevenson

Authors
  1. Reymond E. Sawaya
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  2. Masaaki Yamamoto
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  3. Ziya L. Gokaslan
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  4. Shang Wu Wang
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  5. Sanjeeva Mohanam
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  6. Gregory N. Fuller
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  7. Ian E. McCutcheon
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  8. William G. Stetler-Stevenson
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  9. Garth L. Nicolson
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  10. Jasti S. Rao
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Sawaya, R.E., Yamamoto, M., Gokaslan, Z.L. et al. Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo . Clin Exp Metast 14, 35–42 (1996). https://doi.org/10.1007/BF00157684

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  • DOI: https://doi.org/10.1007/BF00157684

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