TY - JOUR
T1 - Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo
AU - Sawaya, Reymond E.
AU - Yamamoto, Masaaki
AU - Gokaslan, Ziya L.
AU - Wang, Shang Wu
AU - Mohanam, Sanjeeva
AU - Fuller, Gregory N.
AU - McCutcheon, Ian E.
AU - Stetler-Stevenson, William G.
AU - Nicolson, Garth L.
AU - Rao, Jasti S.
PY - 1996
Y1 - 1996
N2 - 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.
AB - 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.
KW - 72 kDa type IV collagenase
KW - Glioblastoma multiforme
KW - Invasiveness
KW - Malignant astrocytoma
KW - Matrix metalloproteinase
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U2 - 10.1007/BF00157684
DO - 10.1007/BF00157684
M3 - Article
C2 - 8521615
AN - SCOPUS:0030033501
SN - 0262-0898
VL - 14
SP - 35
EP - 42
JO - Clinical and Experimental Metastasis
JF - Clinical and Experimental Metastasis
IS - 1
ER -