Heterogeneous regional expression patterns of matrix metalloproteinases in human malignant gliomas.
The aim of the study was to assess the differential intra- and intertumoral heterogeneity and patterns of matrix metalloproteinase expression in human glioblastomas in vivo. 12 glioblastoma samples were analyzed for MMP expression by semi-quantitative RT-PCR. A total of 56 samples (8 adjoining regions of 6 glioblastoma tumors) were immunohistochemically examined for the expression and regional distribution of gelatinase-A (MMP-2), gelatinase-B (MMP-9), matrilysin (MMP-7) and stromelysin-1 (MMP-3). Gelatinase-A mRNA was detected in all samples, gelatinase-B was found in numerous samples. Correspondingly, strong expression levels of both gelatinase protein was seen in immunohistochemistry. Gelatinase-A was expressed by both tumor cells and endothelium while gelatinase-B was found to be restricted to endothelial cells. Stromelysin-1 protein was not detected in any of the samples. Matrilysin was found around tumor cells of three samples from one patient only. The strong immunoreactivity seen for gelatinase-A around tumor cells and blood vessels suggests a role in both tissue degradation and tumor neoangiogenesis which is in accordance with previously published in vitro data. The marked localization of gelatinase-B to the endothelium and its presence in non-infiltrative benign lesions, however, makes a direct proteolytic role of gelatinase-B on ECM components during glioma invasion appear unlikely. Its close association with vascular structures, however, might indicate a link to neoangiogenesis. The significance of matrilysin which was only seen in tumor cells in three samples remains unclear. Stromelysin-1, though strongly expressed in cell lines, does not appear to play a role in glioblastoma tumors in vivo.
Vince
G H
GH
Department of Neurosurgery, Institute of Pathology, University of Wuerzburg, Germany. vince@mail.uni-wuerzburg.de
Wagner
S
S
Pietsch
T
T
Klein
R
R
Goldbrunner
R H
RH
Roosen
K
K
Tonn
J C
JC
D001932:Brain Neoplasms / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D020782:Matrix Metalloproteinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020782:Matrix Metalloproteinases