Stimulation of tPA-dependent provisional extracellular fibrin matrix degradation by human recombinant soluble melanotransferrin.
Tissue-type plasminogen activator (tPA) and its substrate plasminogen (Plg) are key components in the fibrinolytic system. We have recently demonstrated, that truncated human recombinant soluble melanotransferrin (sMTf) could stimulate the activation of Plg by urokinase plasminogen activator and inhibit angiogenesis. Since various angiogenesis inhibitors were shown to stimulate tPA-mediated plasminogen activation, we examined the effects of sMTf on tPA-dependent fibrinolysis. This study demonstrated that sMTf enhanced tPA-activation of Plg by 6-fold. sMTf also increased the release of [125I]-fibrin fragments by tPA-activated plasmin. Moreover, we observed that the interaction of sMTf with Plg provoked a change in the fibrin clot structure by cleaving the fibrin alpha and beta chains. Overall, the present study shows that sMTf modulates tPA-dependent fibrinolysis by modifying the clot structure. These results also suggest that sMTf properties could involve enhanced dissolution of the provisional extracellular fibrin matrix.
Bertrand
Y
Y
Laboratoire de Médecine Moléculaire, Service d'Hématologie-Oncologie, Hôpital Ste-Justine-UQAM, C.P. 8888, Succursale Centre-ville, Montréal, Québec, Canada H3C 3P8.
Demeule
M
M
Rivard
G-E
GE
Béliveau
R
R
D000951:Antigens, Neoplasm; D002478:Cells, Cultured; D003018:Clot Retraction; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005109:Extracellular Matrix / Q000378:metabolism*; D005337:Fibrin / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins / Q000494:pharmacology*; D010958:Plasminogen / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
D000951:Antigens, Neoplasm; D058950:Melanoma-Specific Antigens; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D005337:Fibrin; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin