Expression of tissue factor pathway inhibitor 2 inversely correlates during the progression of human gliomas.
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 Mr 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.
Rao
C N
CN
Department of Neurosurgery, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Lakka
S S
SS
Kin
Y
Y
Konduri
S D
SD
Fuller
G N
GN
Mohanam
S
S
Rao
J S
JS
D001254:Astrocytoma / Q000378:metabolism; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005910:Glioma / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D017403:In Situ Hybridization; D007797:Laminin / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism; D011509:Proteoglycans / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004338:Drug Combinations; D006023:Glycoproteins; D007797:Laminin; D011509:Proteoglycans; D012333:RNA, Messenger; D011994:Recombinant Proteins; C021240:tissue-factor-pathway inhibitor 2; C059485:matrigel; D003094:Collagen