Urinary trypsin inhibitor suppresses surgical stress-facilitated lung metastasis of murine colon 26-L5 carcinoma cells.
Recently, we have reported that surgical stress promoted the metastasis of murine colon carcinoma cells to the lung by inducing the expression of proteases such as matrix metalloprotease-9 (MMP-9) in lung tissue. Urinary trypsin inhibitor (UTI) is a serine protease inhibitor frequently used to treat pancreatitis and to improve the microcirculatory environment. The purpose of this study was to investigate the anti-metastatic properties of UTI in an animal model of surgical stress-induced cancer metastasis. The intraperitoneal administration of UTI after the intravenous injection of colon 26-L5 carcinoma (colon 26-L5) cells into mice subjected to surgical stress suppressed the enhancement of lung metastasis (p<0.05). Furthermore, we investigated the effect of UTI on tumor growth, adhesion to fibronectin, migration, invasion and enzymatic degradation in colon 26-L5. UTI reduced the invasive ability and the degradation by MMP-9 of gelatin substrate in colon 26-L5 cells. UTI may improve therapeutic efficacy in cancer patients after major surgery.
Yoshioka
Isaku
I
Second Department of Surgery, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani Toyama 930-0194, Japan.
Tsuchiya
Yasunori
Y
Aozuka
Yasushi
Y
Onishi
Yasuharu
Y
Sakurai
Hiroaki
H
Koizumi
Keiichi
K
Tsukada
Kazuhiro
K
Saiki
Ikuo
I
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D048708:Cell Growth Processes / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D003110:Colonic Neoplasms / Q000201:enzymology / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000201:enzymology / Q000517:prevention & control* / Q000556:secondary*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008807:Mice, Inbred BALB C; D009361:Neoplasm Invasiveness; D013312:Stress, Physiological / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D014361:Trypsin Inhibitors / Q000494:pharmacology
D006023:Glycoproteins; D061965:Matrix Metalloproteinase Inhibitors; D014361:Trypsin Inhibitors; D020780:Matrix Metalloproteinase 9; C028665:urinastatin