Amiloride and urinary trypsin inhibitor inhibit urothelial cancer invasion.
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.
Oka
Natsuo
N
Department of Urology, The University of Tokushima School of Medicine, 3-18-15, Kuramoto-Cho, Tokushima 770-8503, Japan.
Okumura
Yuushi
Y
Kanayama
Hiro-Omi
HO
Izaki
Hirofumi
H
Okamoto
Masumi
M
Kido
Hiroshi
H
Kagawa
Susumu
S
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
D012333:RNA, Messenger; D014361:Trypsin Inhibitors; D000584:Amiloride; D014568:Urokinase-Type Plasminogen Activator