Activation of pro-uPA is critical for initial escape from the primary tumor and hematogenous dissemination of human carcinoma cells.

ABSTRACT: Urokinase-type plasminogen activator (uPA) and plasmin have long been implicated in cancer progression. However, the precise contributions of the uPA/plasmin system to specific steps involved in cancer cell dissemination have not been fully established. Herein, we have used a highly disseminating variant of the human PC-3 prostate carcinoma cell line, PC-hi/diss, as a prototype of aggressive carcinomas to investigate the mechanisms whereby pro-uPA activation and uPA-generated plasmin functionally contribute to specific stages of metastasis. The PC-hi/diss cells secrete and activate significant amounts of pro-uPA, leading to efficient generation of plasmin in solution and at the cell surface. In a mouse orthotopic xenograft model, treatment with the specific pro-uPA activation-blocking anti

SUBMITTER: Bekes EM 

PROVIDER: S-EPMC3182273 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature