Gelatinase-A (MMP-2), gelatinase-B (MMP-9) and membrane type matrix metalloproteinase-1 (MT1-MMP) are involved in different aspects of the pathophysiology of malignant gliomas

Matrix metalloproteinases (MMPs) have been implicated as important factors in gliomas since they may both facilitate invasion into the surrounding bra in and participate in neovascularization. We have tested the hypothesis tha t deregulated expression of gelatinase-A or B, or an activator of gelatinas e-A, MT1-MMP, may contribute directly to human gliomas by quantifying the e xpression of these MMPs in 46 brain tumour specimens and seven control tiss ues. Quantitative RT-PCR and gelatin zymography showed that gelatinase-A in glioma specimens was higher than in normal tissue; these were significantl y elevated in low grade gliomas and remained elevated in GBMs. Gelatinase-B transcript and activity levels were also higher than in normal brain and m ore strongly correlated with tumour grade, We did not see a close relations hip between the levels of expression of MT1-MMP mRNA and amounts of activat ed gelatinase-A, In situ hybridization localized gelatinase-A and MT1-MMP t ranscripts to normal neuronal and glia, malignant glioma cells and blood ve ssels. In contrast, gelatinase-B showed a more restricted pattern of expres sion; it was strongly expressed in blood vessels at proliferating margins, as well as tumour cells in some cases. These data suggest that gelatinase-A , -B and MT1-MMP are important in the pathophysiology of human gliomas. The primary role of gelatinase-B may lie in remodelling associated with neovas cularization, whereas gelatinase-A and MT1-MMP may be involved in both glia l invasion and angiogenesis.