Inhibitory effect on the establishment of hepatic metastasis by transduction of the tissue plasminogen activator gene to murine colon cancer.
Hepatic metastasis is a major factor in limiting the prognosis of patients with colon carcinoma. Recent investigations indicate a correlation between plasminogen activator profiles and hepatic metastasis. We examined the effectiveness of tissue plasminogen activator (tPA) gene therapy using a hepatic metastasis model of murine colon carcinoma. Murine colon carcinoma Colon 26 cells transduced with an MFGtPA retroviral vector (Colon 26/tPA) or an MFGLacZ retroviral vector (Colon 26/LacZ) were injected into the liver via the superior mesenteric vein of BALB/c mice, whose survival rates were checked daily. The mean survival rate of mice with hepatic metastasis induced by Colon 26/LacZ was 23.1 days, whereas that of mice with Colon 26/tPA was >100 days. The in vitro proliferation of Colon 26/tPA was comparable with that of Colon 26/LacZ, and antitumor immunity to wild-type Colon 26 cells was not induced after an intrahepatic injection of Colon 26/tPA. We suggest that transduction of the tPA gene to murine colon cancer is useful against the establishment of hepatic metastasis.
Department of Surgery II, Nagoya University School of Medicine, Japan.
S
S
Hayashi
I
I
Yokoyama
Y
Y
Namii
N
N
Emi
K
K
Uchida
H
H
Takagi
D000818:Animals; D002455:Cell Division / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015316:Genetic Therapy; D005822:Genetic Vectors; D008114:Liver Neoplasms, Experimental / Q000517:prevention & control* / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D010534:Peritoneal Neoplasms / Q000517:prevention & control / Q000556:secondary; D012190:Retroviridae / Q000235:genetics; D015996:Survival Rate; D010959:Tissue Plasminogen Activator / Q000235:genetics*
D010959:Tissue Plasminogen Activator