Expression and localization of 72 kDa type IV collagenase (MMP-2) in human malignant gliomas in vivo.
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.
Sawaya
R E
RE
Department of Neurosurgery, University of Texas, M. D. Anderson Cancer Center, Houston 77030, USA.
Yamamoto
M
M
Gokaslan
Z L
ZL
Wang
S W
SW
Mohanam
S
S
Fuller
G N
GN
McCutcheon
I E
IE
Stetler-Stevenson
W G
WG
Nicolson
G L
GL
Rao
J S
JS
D000595:Amino Acid Sequence; D001254:Astrocytoma / Q000378:metabolism; D015152:Blotting, Northern; D001923:Brain Chemistry; D001932:Brain Neoplasms / Q000737:chemistry* / Q000378:metabolism*; D018450:Disease Progression; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay; D018093:Gelatinases / Q000032:analysis* / Q000378:metabolism* / Q000502:physiology; D005910:Glioma / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D020778:Matrix Metalloproteinase 2; D008666:Metalloendopeptidases / Q000032:analysis* / Q000378:metabolism* / Q000502:physiology; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis
D012333:RNA, Messenger; D018093:Gelatinases; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2