Chapter category: Cancer Metastasis
The Plasminogen Activation System in Cell Invasion
Cell Invasion
Edited by: Jyrki Heino and Veli-Matti KähäriISBN: 1-58706-073-6
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Chapter authors:
M. Patrizia Stoppelli
The plasminogen activator/plasmin system is an enzymatic cascade involved in the control of fibrin degradation, matrix turnover and cell invasion.
Extracellular conversion of the ubiquitous inactive plasminogen to the broad spectrum serine protease plasmin results in the recruitment of an enormous reservoir of potential proteolytic activity. Plasmin is, in turn, able to degrade fibronectin, laminin, vitronectin, proteoglycans, as well as fibrin and activate latent collagenases. Plasminogen activation is catalyzed by urinary (uPA) or tissuetype (tPA) plasminogen activators (PAs), which are subjected to time and spacedependent regulation. In particular, uPA is regarded as the critical trigger for plasmin generation during cell migration and invasion, under physiological and pathological conditions (such as cancer metastasis), whereas tPA is likely to play an important role in the control of intravascular fibrin degradation. The system includes specific plasminogen activator inhibitors (PAIs) which counteract the activity of PAs, thereby restricting the generation of plasmin for extracellular matrix (ECM) as well as for intravascular fibrin degradation.
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