EFFECTS OF SURAMIN ON METASTATIC ABILITY, PROLIFERATION, AND PRODUCTION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND PLASMINOGEN-ACTIVATOR INHIBITOR TYPE-2 IN HUMAN RENAL-CELL CARCINOMA CELL-LINE SN12C-PM6

Effects of suramin, a polysulfonated naphthylurea compound, on metasta tic ability, proliferation, and production of plasminogen activators a nd plasminogen activator inhibitors were studied using the highly meta static human renal cell carcinoma cell line, SN12C-PM6. After renal su bscapular implantation of tumor cells in nude mice, suramin significan tly inhibited metastasis of tumor cells to the lungs and liver. In vit ro growth of tumour cells was inhibited by suramin in a dose-dependent manner, at relatively low doses (ID50 = 105 mu g/ml). Plasminogen act ivator inhibitor type 2 (PAI-2) production by tumor cells was enhanced by suramin (100 mu g/ml), whereas urokinase-type plasminogen activato r (uPA) production was suppressed. Thus, the increase in PAI-2 and the decrease in uPA production correlated with the inhibitory effects on tumour growth and metastasis by suramin. Therefore suramin may be bene ficial for the treatment of patients with an early stage of renal canc er with potential risk of metastasis.