PLASMIN MODULATORS, APROTININ AND ANTI-CATALYTIC PLASMIN ANTIBODY, EFFICIENTLY INHIBIT DESTRUCTION OF BOVINE VASCULAR ENDOTHELIAL-CELLS BY CHORIOCARCINOMA CELLS

The interaction of human gestational choriocarcinoma cell line, SMT-cc 1, with bovine vascular endothelial cells, CPAE, was examined in an in vitro coculture model. SMT-cc1 cells have urokinase-type plasminogen activator (uPA) on their cell surface, and more than half of the cell- associated uPA is enzymatically inactive single-chain uPA (pro-uPA). u PA is bound to a specific surface receptor that is not completely satu rated. Also, the plasmin activity is detected on their cell surface. W e measured the ability of added SMT-cc1 cells to cause morphological c hanges in CPAE cells, leading to destruction of CPAE cells. SMT-cc1 ce lls that adhered to CPAE cell monolayers were capable of causing CPAE cell destruction, followed by detachment, within 6 hr after coculture. Nonspecific serine proteinase inhibitor, aprotinin, and anti-catalyti c antibody against plasmin(ogen) effectively inhibited the destruction /detachment in a dose-dependent manner. SMT-cc1 cell-mediated CPAE cel l destruction was suppressed for 6 hr in the presence of aprotinin, at a concentration of 20 mug/ml, or anti-plasmin antibody, at a concentr ation of greater-than-or-equal-to 10 mug/ml, suggesting that the destr uction is closely related to the proteolytic enzyme, plasmin. We sugge st that the destruction of endothelial cells by some tumor cells is as sociated with tumor cell-associated proteolytic activity, and the uPA- plasmin cascade plays an important role as a critical step during bloo d-borne metastasis. (C) 1994 Academic Press, Inc.