Urokinase‐type plasminogen activator and its receptor in colorectal cancer: Independent prognostic factors of metastasis and cancer‐specific survival and potential therapeutic targets

摘要: Urokinase-type plasminogen activator (uPA) and its receptor (uPAR), (Plg), inhibitors-1 -2 (PAI-1 PAI-2) have been observed in many cancers may contribute to progression metastasis. In our study, we examined the expression of 5 proteins by immunohistochemistry 59 consecutive primary colorectal (CRC) correlated protein with patient outcome. addition, determined effect down-regulation uPAR on invasive/metastatic capability CRC cells, measuring antisense-uPAR transfected HCT116 control cell lines, terms expression, uPA-binding activity, invasiveness through Matrigel vitro metastasis after cecal orthotopic implantation nude mice vivo. We found that higher uPA or tumor tissues was positively distant (Mann-Whitney, p < 0.02) negatively both overall survival (OS) cancer-specific (CSS; Cox model, 0.04). The prognostic value for OS CSS independent other variables (multivariate 0. 007). Antisense-uPAR which expressed significantly lower levels total cellular surface activity compared either wild-type cells vector alone (Bonferroni, 0.05/3), consistently showed decreased 0.05/3) formation (Fisher, 0.05). Our data suggest are factors CRC; anti-uPAR treatment, affects levels, potential new treatment disease.