Overexpression of tissue factor pathway inhibitor-2 (TFPI-2), decreases the invasiveness of prostate cancer cells in vitro.
Human tissue factor pathway inhibitor-2 (TFPI-2) is a 32-kDa serine protease inhibitor that inhibits plasmin, trypsin, chymotrypsin, cathepsin G, and plasma kallikrein but not urokinase and tissue-type plasminogen activators or thrombin. After discovering that TFPI-2 expression is down-regulated or lost during tumor progression, we investigated the role of TFPI-2 in the invasiveness of the prostate cancer cell line (LNCaP). We stably transfected LNCaP cells with a 0.7-kb vector expressing TFPI-2 in the sense orientation and measured the expression of TFPI-2 protein and mRNA by these cells by western and northern blotting. Neither TFPI-2 protein nor mRNA was expressed by parental LNCaP cells or vector-transfected controls, but levels of both protein and mRNA were significantly increased in the sense-TFPI-2 clones. The sense clones were less invasive than the control cells in Matrigel invasion and spheroid migration assays. This is the first demonstration that upregulation of TFPI-2 plays a significant role in the invasive behavior of human prostate cancer cells.
Konduri
S D
SD
Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Tasiou
A
A
Chandrasekar
N
N
Rao
J S
JS
D001672:Biocompatible Materials; D015415:Biomarkers; D015152:Blotting, Northern; D002465:Cell Movement / Q000502:physiology; D003094:Collagen / Q000502:physiology; D004338:Drug Combinations; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007797:Laminin / Q000502:physiology; D008297:Male; D009361:Neoplasm Invasiveness; D011257:Pregnancy Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D011509:Proteoglycans / Q000502:physiology; D018874:Spheroids, Cellular / Q000473:pathology; D014162:Transfection; D014407:Tumor Cells, Cultured
D001672:Biocompatible Materials; D015415:Biomarkers; D004338:Drug Combinations; D006023:Glycoproteins; D007797:Laminin; D011257:Pregnancy Proteins; D011509:Proteoglycans; C021240:tissue-factor-pathway inhibitor 2; C059485:matrigel; D003094:Collagen