Independent regulation of matrix metalloproteinases and plasminogen activators in human fibrosarcoma cells.
Serine proteases and matrix metalloproteinases have been shown to often cooperate in multiple physiological and pathological processes associated with changes in the extracellular matrix (ECM). We have examined the interaction between the plasminogen activator (PA)-plasmin system and matrix metalloproteinases (MMPs) in HT1080 human fibrosarcoma cells treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). While TPA treatment evoked a temporary increased expression of urokinase type PA (uPA), the production of both types of human plasminogen activator inhibitors (PAI) was induced and sustained over 12 h by TPA treatment shifting the protease-protease inhibitors balance in favor of the inhibitors. TPA treatment of HT1080 cells induced the expression of interstitial collagenase (MMP-1) and increased the expression of gelatinase B (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1), and MT-MMP, a membrane-bound activator of progelatinase A (proMMP-2), while MMP-2 and TIMP-2 expression were decreased. Increased MT-MMP expression by TPA treatment was associated with increased activation of proMMP-2. These data show that the regulation of PA-plasmin and metalloproteinase and their specific inhibitors is uncoordinated. In addition, inhibition of the PA-plasmin system by PAI-2 or aprotinin did not prevent the activation of proMMP-2 by TPA, suggesting that plasmin is not involved in MT-MMP-mediated activation of proMMP-2.
Lim
Y T
YT
Department of Pediatrics, Pusan National University, Korea.
Sugiura
Y
Y
Laug
W E
WE
Sun
B
B
Garcia
A
A
DeClerck
Y A
YA
D007611:Aprotinin / Q000494:pharmacology; D015152:Blotting, Northern; D002273:Carcinogens / Q000494:pharmacology; D017364:Collagenases / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D005341:Fibrinolysin / Q000494:pharmacology; D005343:Fibrinolytic Agents / Q000494:pharmacology; D005354:Fibrosarcoma / Q000201:enzymology*; D018093:Gelatinases / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D017396:Plasminogen Activator Inhibitor 2 / Q000494:pharmacology; D010960:Plasminogen Activators / Q000096:biosynthesis* / Q000235:genetics; D011480:Protease Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D019716:Tissue Inhibitor of Metalloproteinase-2; D014407:Tumor Cells, Cultured / Q000201:enzymology
D002273:Carcinogens; D004792:Enzyme Precursors; D005343:Fibrinolytic Agents; D017396:Plasminogen Activator Inhibitor 2; D011480:Protease Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D019716:Tissue Inhibitor of Metalloproteinase-2; D007611:Aprotinin; D010960:Plasminogen Activators; D005341:Fibrinolysin; D017364:Collagenases; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1; D013755:Tetradecanoylphorbol Acetate