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Tumor Biology |
Departments of Oncology (S.A.R., H.M.), Clinical Neurosciences (S.A.R., H.M., P.A.F.), Medical Biochemistry (R.N.J.), and Pediatrics (P.A.F.), The University of Calgary, Calgary, Alberta, Canada T2N 4N1; Department of Pathology, Foothills Hospital, Calgary, Alberta, Canada, T2N 2T9 (N.B.R.); School of Biological Sciences, University of East Anglia, Norwich, Norfolk, England NR4 7TJ (D.R.E.); and the Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada T2N 4N2 (P.A.F.)
1 Address correspondence and reprint requests to Peter Forsyth, Tom Baker Cancer Centre, 1331 29th St. N.W., Calgary, Alberta, Canada.
Abstract
Malignant gliomas maintain a poor prognosis and survival rate due to their marked local invasive growth and neovascularization. Matrix metalloproteinases (MMPs) have been implicated in glioma invasion and angiogenesis, but it is unknown whether they are produced by the tumor cells or surrounding stroma. Using in situ hybridization and immunohistochemistry, we found expression of mRNA for both gelatinase-A (MMP2) and gelatinase-B (MMP9) localized to tumor cells and vascular structures in glioma sections. Gelatinase-A protein expression was detected most prominently in tumor cells, with very little signal seen in vasculature. Gelatinase-B protein expression was prominent in vascular structures but was also expressed in tumor cells. Our data show that these proteases are produced by glioma cells and vascular structures and suggest that synthetic MMP inhibitors might be useful in this disease.
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