Expression of Tissue Factor Pathway Inhibitor 2 Inversely Correlates during the Progression of Human Gliomas

• Published in: Clinical cancer research Vol. 7; no. 3; pp. 570 - 576
• Main Authors: RAO, Chilukuri N, LAKKA, Sajani S, KIN, Yoshiaki, KONDURI, Santhi D, FULLER, Gregory N, MOHANAM, Sanjeeva, RAO, Jasti S
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01-03-2001
• Subjects: Astrocytoma - metabolism; Biological and medical sciences; Blotting, Northern; Blotting, Western; Brain - metabolism; Brain Neoplasms - metabolism; Collagen - pharmacology; Disease Progression; DNA, Complementary - metabolism; Dose-Response Relationship, Drug; Drug Combinations; Glioma - metabolism; Glycoproteins - biosynthesis; Humans; In Situ Hybridization; Laminin - pharmacology; Medical sciences; Neurology; Neurons - metabolism; Proteoglycans - pharmacology; Recombinant Proteins - metabolism; RNA, Messenger - metabolism; Tumor Cells, Cultured; Tumors of the nervous system. Phacomatoses; Histological grading; Gene product; Tumoral tissue; Tissue factor; Biological marker; Metastasis; Angiogenesis; Malignant glioma; Established cell line; Tumor progression; Tumor cell; Human; Intracranial; Nervous system diseases; Enzyme; Enzyme inhibitor; Malignant tumor; Gene expression; In vitro; Invasion; Cerebral disorder; Serine enzyme; Peptidases; Central nervous system disease; Hydrolases
• ISSN: 1078-0432; 1557-3265

Protease inhibitors regulate a variety of physiological and pathological processes including angiogenesis, embryo implantation,
intravascular fibrinolysis, wound healing, and tumor invasion. Tissue factor pathway inhibitor (TFPI) 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 thrombin. In this study, we determined the
relative amounts of TFPI-2 in low-, intermediate-, and high-grade human glioma cell lines and tumor tissue samples. TFPI-2
protein and mRNA levels (measured by Western and Northern blotting) were highest in low-grade glioma cells (Hs683), lower
in anaplastic astrocytoma cells (SW1088 and SW1783), and undetectable in high-grade glioma cells (SNB19). Analysis of TFPI-2
protein in human normal brain and in glioma tumor tissues for TFPI-2 revealed the highest levels in normal brain, lesser amounts
in low-grade gliomas and anaplastic astrocytomas, and undetectable amounts in glioblastomas. In situ hybridization of TFPI-2 mRNA with normal brain tissues revealed the greatest positivity in neurons, with moderate positivity
in both glial and endothelial cells and moderate, little, or no TFPI-2 mRNA in low-grade glioma, anaplastic astrocytoma, and
glioblastoma tumor tissue samples, respectively. We also found that recombinant TFPI-2 inhibited the invasiveness 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 in vitro and in vivo .