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

Reymond E. Sawaya, Masaaki Yamamoto, Ziya L. Gokaslan, Shang Wu Wang, Sanjeeva Mohanam, Gregory N. Fuller, Ian E. McCutcheon, William G. Stetler-Stevenson, Garth L. Nicolson, Jasti S. Rao

Research output: Contribution to journalArticlepeer-review

162 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)35-42
Number of pages8
JournalClinical and Experimental Metastasis
Issue number1
StatePublished - 1996
Externally publishedYes


  • 72 kDa type IV collagenase
  • Glioblastoma multiforme
  • Invasiveness
  • Malignant astrocytoma
  • Matrix metalloproteinase

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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