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| The EMBO Journal
(1997) 16, 2319–2332, doi:10.1093/emboj/16.9.2319 |
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| Control of type IV collagenase activity by components of the urokinase–plasmin system: a regulatory mechanism with cell-bound reactants |
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| Roberta Mazzieri1, Laura Masiero2, Lucia Zanetta1, Sara Monea1, Maurizio Onisto2, Spiridione Garbisa2 and Paolo Mignatti1, 3 |
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1 Dipartimento di Genetica e Microbiologia, Università di Pavia, 27100 Pavia, Italy 2 Istituto di Istologia ed Embriologia, Università di Padova, 35121 Padova, Italy 3 Present address: Departments of Surgery and Cell Biology, New York University Medical Center, 550 First Avenue, New York, NY 10016, USA To whom correspondence should be addressed Paolo Mignatti, mignap01@mcrcr.med.nyu.edu Received 6 May 1996; Revised 4 December 1996. |
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| Abstract |
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| The urokinase-type plasminogen activator (uPA) and the matrix-degrading metalloproteinases MMP-2 and MMP-9 (type IV collagenases/gelatinases) have been implicated in a variety of invasive processes, including tumor invasion, metastasis and angiogenesis. MMP-2 and MMP-9 are secreted in the form of inactive zymogens that are activated extracellularly, a fundamental process for the control of their activity. The physiological mechanism(s) of gelatinase activation are still poorly understood; their comprehension may provide tools to control cell invasion. The data reported in this paper show multiple roles of the uPA–plasmin system in the control of gelatinase activity: (i) both gelatinases are associated with the cell surface; binding of uPA and plasmin(ogen) to the cell surface results in gelatinase activation without the action of other metallo- or acid proteinases; (ii) inhibition of uPA or plasminogen binding to the cell surface blocks gelatinase activation; (iii) in soluble phase plasmin degrades both gelatinases; and (iv) gelatinase activation and degradation occur in a dose- and time-dependent manner in the presence of physiological plasminogen and uPA concentrations. Thus, the uPA–plasmin system may represent a physiological mechanism for the control of gelatinase activity. |
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| Keywords: activation, cell surface, gelatinase, plasmin, urokinase |
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