Expression of matrix metalloproteinases, their inhibitors, and urokinase plasminogen activator in human meningiomas.
MMP-2, MMP-9, and uPA have been previously described as important to the invasive and metastatic potential of human tumors, including breast, lung, glioblastoma, and prostate. We examined the activity of these proteases and the levels of their inhibitors (TIMP-1 and TIMP-2) in a series of human meningioma tissue samples. Normal brain tissue did not show elevated levels of uPA, MMP-2 or MMP-9 activity. Meningiomas showed a mild, to moderate to significantly high level of uPA, MMP-2, and MMP-9. However, no increase in TIMP-1 or TIMP-2 levels was detected. Immunohistochemistry confirmed the assay findings and localized these molecules to the cell surface. The findings provide evidence for elevated levels of uPA and MMPs in meningiomas and suggest a therapeutic target for minimizing the malignant propensity of meningiomas using protease inhibitors.
Siddique
Khawar
K
Department of Neurosurgery, University of Illinois College of Medicine at Peoria, IL 61656, USA.
Yanamandra
Niranjan
N
Gujrati
Meena
M
Dinh
Dzung
D
Rao
Jasti S
JS
Olivero
William
W
D001921:Brain / Q000378:metabolism; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis* / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics
D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9