Cellular and extracellular plasminogen activator and inhibitor in an experimental tumour.
We determined plasminogen activator (PA) and PA inhibitor (PAI) activities in the intra- and extracellular compartments of an experimental pancreatic ascites tumour with indirect and direct functional assays, and partially characterized these activities on SDS-polyacrylamide gels coupled with fibrin and reverse fibrin autography. Intact tumour cells caused lysis of plasminogen-rich but not plasminogen-free fibrin clots, and the extent of lysis of the former was related to tumour cell count. Direct assay of PA with a synthetic substrate yielded an equivalent of 109 urokinase units per 10(9) tumour cells. No PAI activity was demonstrated in tumour cells with functional assays. Contrary to tumour cells, cell-free ascitic fluids caused no lysis of fibrin clots. Instead, it inhibited tumour cell- and urokinase-induced, but not plasmin-induced, clot lysis in a dose-dependent fashion. Although functional assays failed to demonstrate PA in ascitic fluid and PAI in tumour cells, both activities were detected in electrophoresed samples of cell lysates and fluids by fibrin and reverse fibrin autography. In tumour cells, a mixture of tissue-type PA (tPA) and urokinase-type PA (uPA) were present. In the fluid, uPA together with two other PAs with greater molecular weights than tPA were detected.
D000818:Animals; D001202:Ascitic Fluid / Q000032:analysis; D002452:Cell Count; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D005342:Fibrinolysis; D006023:Glycoproteins / Q000378:metabolism; D008647:Mesocricetus; D010190:Pancreatic Neoplasms / Q000201:enzymology*; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015849:Plasminogen Inactivators; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator