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-cc1, 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). uPA is bound to a specific surface receptor that is not completely saturated. Also, the plasmin activity is detected on their cell surface. We measured the ability of added SMT-cc1 cells to cause morphological changes in CPAE cells, leading to destruction of CPAE cells. SMT-cc1 cells 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-catalytic antibody against plasmin(ogen) effectively inhibited the destruction/detachment in a dose-dependent manner. SMT-cc1 cell-mediated CPAE cell destruction was suppressed for 6 hr in the presence of aprotinin, at a concentration of 20 micrograms/ml, or anti-plasmin antibody, at a concentration of > or = 10 micrograms/ml, suggesting that the destruction is closely related to the proteolytic enzyme, plasmin. We suggest that the destruction of endothelial cells by some tumor cells is associated with tumor cell-associated proteolytic activity, and the uPA-plasmin cascade plays an important role as a critical step during blood-borne metastasis.
Sugimura
M
M
Department of Obstetrics and Gynecology, Hamamatsu University School of Medicine, Shizuoka, Japan.
Kobayashi
H
H
Terao
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D007611:Aprotinin / Q000494:pharmacology*; D002417:Cattle; D002450:Cell Communication; D002478:Cells, Cultured; D002822:Choriocarcinoma / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005341:Fibrinolysin / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D006801:Humans; D011247:Pregnancy; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000502:physiology; D014594:Uterine Neoplasms / Q000473:pathology*
D000911:Antibodies, Monoclonal; D007611:Aprotinin; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator