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

✍ Scribed by 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

• Publisher: Springer
• Year: 1996
• Tongue: English
• Weight: 750 KB
• Volume: 14
• Category: Article
• ISSN: 0262-0898
• DOI: 10.1007/bf00157684

✦ Synopsis

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.