Matrix metalloproteinases in human gliomas: Activation of matrix metalloproteinase-2 (MMP-2) may be correlated with membrane-type-1 matrix metalloproteinase (MT1-MMP) expression

To evaluate possible roles of matrix metalloproteinase (MMP)-1, -2, tissue inhibitor of metalloproteinase (TIMP)-1, -2 and membrane-type-1 matrix meta lloproteinase (MT1-MMP) in invasion of human gliomas, expressions of these proteins were investigated in ten cases of human glioma and two meningioma tissues and eight human glioma cell lines. In gelatin zymography, MMP-2 act ivities of glioblastomas were higher than astrocytomas, The activated form of MMP-2 was seen in five of six cases of glioblastomas, but not in astrocy tomas. MMP-9 activity was detected in all cases of malignant astrocytomas b ut the reactivity of MMP-9 was weaker than that of MMP-2. MT1-MMP mRNA expr ession in glioblastomas was higher than that in astrocytomas. Five cases of glioblastomas with activated form of MMP-2 had MT1-MMP expressions. In vit ro, human glioma cell lines with high expression of MT1-MMP also showed hig h MMP-2 activity. TIMP-1 transcripts were constitutively present in almost all glioma tissues and cell lines, whereas TIMP-2 mRNA were weak especially in malignant gliomas. Imbalance of TIMP-2/MMP-2 was observed using immunop recipitation analysis in a glioma cell line, High expression of MMP-2 and M T1-MMP is possibly involved in invasiveness of malignant glioma.