Matrix plasminogen activator inhibitor. Modulation of the extracellular proteolytic environment.
We have previously demonstrated that plasminogen activator inhibitor (PAI-1) is associated with the extracellular matrix of cultured bovine smooth muscle cells (Knudsen, B.S., Harpel, P.C., Nachman, R.L. (1987) J. Clin. Invest. 80, 1082-1089). In this report we describe the physiologic role of PAI-1 during the interaction of the tissue plasminogen activator (t-PA) secreting Bowes human melanoma cell line with endothelial extracellular matrices. In addition we have characterized the t-PA.PAI complexes formed during this interaction in the presence and absence of plasminogen. In the absence of plasminogen, a 104-kDa complex between Bowes t-PA and PAI-1 appears in the supernatant. In the presence of plasminogen, PAI initially prevents plasmin formation on the matrix and protects the matrix from degradation by plasmin. The 104-kDa t-PA.PAI complex is degraded into a 68 and a 47-kDa complex by small amounts of plasmin generated from secreted Bowes t-PA and plasminogen. Analysis of these complexes revealed that t-PA is rapidly cleaved by plasmin within the complex whereas complexed PAI-1 is not further degraded. Matrix-associated PAI-1 may play an important role in the protection of extracellular matrices from remodeling and degradation by cellular t-PA and plasminogen.
Knudsen
B S
BS
Division of Hematology-Oncology, Cornell University Medical College, New York, New York 10021.
Nachman
R L
RL
D002460:Cell Line; D004727:Endothelium / Q000166:cytology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008545:Melanoma; D010958:Plasminogen / Q000378:metabolism; D010960:Plasminogen Activators / Q000037:antagonists & inhibitors*; D015849:Plasminogen Inactivators
D006023:Glycoproteins; D015849:Plasminogen Inactivators; D010958:Plasminogen; D010960:Plasminogen Activators; D005341:Fibrinolysin