title: Amiloride and urinary trypsin inhibitor inhibit urothelial cancer invasion.
abstract: OBJECTIVE
  To determine the contribution of urokinase-type plasminogen activator (uPA) and plasmin in the invasion of highly invasive urothelial cancer cells.
  
  
  METHODS
  We compared expression levels of mRNA and protease activity of uPA and plasmin formation in primary cultures of the noninvasive transitional cell carcinoma, UCT-1, and in the highly invasive type, UCT-2. By using in vitro cell invasion assay system, we evaluated the effects of amiloride and urinary trypsin inhibitor (UTI), which inhibit uPA and plasmin, respectively, on invasion by both cell lines.
  
  
  RESULTS
  Expression levels of mRNA, protein, and activities of uPA were significantly higher (p<0.005) and resulted in more plasminogen activation in UCT-2 than in UCT-1. Amiloride and UTI significantly inhibited plasmin formation and the invasion of both cell lines (p<0.001).
  
  
  CONCLUSIONS
  High expression levels of mRNA, activities of uPA and high plasmin formation significantly potentiated the invasiveness of urothelial cancer cells. Thus, inhibitors of uPA and plasmin, such as amiloride and UTI, respectively, could be useful therapeutic tools with which to treat urothelial cancer.
authors.affiliation: Department of Urology, The University of Tokushima School of Medicine, 3-18-15, Kuramoto-Cho, Tokushima 770-8503, Japan.
authors.forename: Natsuo
authors.initials: N
authors.lastname: Oka
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Okumura
authors.forename: Hiro-Omi
authors.initials: HO
authors.lastname: Kanayama
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Izaki
authors.forename: Masumi
authors.initials: M
authors.lastname: Okamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kido
authors.forename: Susumu
authors.initials: S
authors.lastname: Kagawa
mesh_terms: D000584:Amiloride / Q000494:pharmacology*; D002295:Carcinoma, Transitional Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D014361:Trypsin Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator