Urokinase plasminogen activator (uPA) has been proposed to play a key role in metastatic process of a variety of carcinoma by promoting plasmin mediated tissue degradation. Metastatic cell invasion requires localized proteolysis which could be directed by uPA receptor (uPAR) and a putative plasminogen receptor, alpha-enolase. We have determined invasive potentials of established human uroepithelial cell lines in in vitro assays. The cells were found to be highly invasive (T24, J82, 5637) or slightly invasive (TCCSUP, HT-1376, RT4). The cells were further studied to determine uPAR display on the cell surface, and mRNA expression for uPA, uPAR, alpha-enolase and plasminogen activator inhibitor type-1 (PAI-1). Weakly invasive cells demonstrated a very low quantity 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, resulted in a significant reduction in cellular invasiveness. These results suggest that uPAR and putative plasminogen receptor alpha-enolase are contributors to cellular invasiveness of neoplastic human uroepithelial cells.

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