INVASIVE NEOPLASTIC UROEPITHELIAL CELLS EXPRESS HIGH-LEVELS OF UROKINASE RECEPTOR AND PLASMINOGEN RECEPTOR, ALPHA-ENOLASE

Urokinase plasminogen activator (uPA) has been proposed to play a key role in metastatic process of a variety of carcinoma by promoting plas min mediated tissue degradation. Metastatic cell invasion requires loc alized proteolysis which could be directed by uPA receptor (uPAR) and a putative plasminogen receptor, alpha-enolase. We have determined inv asive potentials of established human uroepithelial cell lines in in v itro assays. The cells were found to be highly invasive (T24, J82, 563 7) or slightly invasive (TCCSUP, HT-1376, RT4). The cells were further studied to determine uPAR display on the cell surface, and mRNA expre ssion for uPA, uPAR, alpha-enolase and plasminogen activator inhibitor type-1 (PAI-1). Weakly invasive cells demonstrated a very low quantit y of uPAR or alpha-enolase-related products, or elevated level of PAI- 1 mRNA. The highly invasive phenotype, however, was associated with an increased level of both uPAR production and alpha-enolase expression. Pretreatment of the highly invasive cells with tranexamic acid, that inhibits binding of both plasminogen and plasmin to the cells, resulte d in a significant reduction in cellular invasiveness. These results s uggest that uPAR and putative plasminogen receptor alpha-enolase are c ontributors to cellular invasiveness of neoplastic human uroepithelial cells.