Expression of tissue factor pathway inhibitor 2 inversely correlates during the progression of human gliomas

Protease inhibitors regulate a variety of physiological and pathological pr ocesses including angiogenesis, embryo implantation, intravascular fibrinol ysis, mound healing, and tumor invasion. Tissue factor pathway inhibitor (T FPI) 2 is a M-r 32,000 Kunitz-type serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase-type plasminogen activator, tissue plasminogen activator, or thro mbin, In this study, we determined the relative amounts of TFPI-2 in low-, intermediates and high-grade human glioma cell Lines and tumor tissue sampl es. TFPI-2 protein and mRNA levels (measured by Western and Northern blotti ng) were highest in low-grade glioma cells (Hs683), lower in anaplastic ast rocytoma cells (SW1088 and SW1783), and undetectable In high-grade glioma c ells (SNB19). Analysis of TFPI-2 protein in human normal brain and in gliom a tumor tissues far TFPI-2 revealed the highest levels in normal brain, les ser amounts in low-grade gliomas and anaplastic astrocytomas, and undetecta ble amounts in glioblastomas. In situ hybridization of TFPI-2 mRNA with nor mal brain tissues revealed the greatest positivity in neurons, with moderat e positivity in both glial and endothelial cells and moderate, little, or n o TFPI-2 mRNA in low-grade glioma, anaplastic astrocytoma, and glioblastoma tumor tissue samples, respectively. We also found that recombinant TFPI-2 inhibited the invasive-ness of SNB19 glioblastoma cells in a Matrigel assay in a dose-dependent manner. Collectively, these results suggest that TFPI- 2 has a regulatory role in the invasiveness of gliomas irt vitro and in viv o.