ABSTRACT
The p lasm inogen activato r/p lasm in system is an enzym atic cascade involved in the con tro l o f fibrin degradation , m atrix tu rnover and cell invasion. Extracellular conversion o f the ub iqu itous inactive plasm inogen to the broad spectrum serine
protease plasm in results in the recru itm en t o f an enorm ous reservoir o f po ten tia l pro teoly tic activity. Plasm in is, in tu rn , able to degrade fib ronectin , lam in in , v itronectin , proteoglycans, as well as fibrin and activate la ten t collagenases. Plasm inogen activation is catalyzed by u rinary (uPA) o r tissue-type (tPA) p lasm inogen activators (PAs), w hich are subjected to tim e and space-dependent regulation. In particular, uPA is regarded as the critical trigger for p lasm in g eneration d u rin g cell m igration an d invasion, u n d e r physiological an d pathological co n d i tions (such as cancer m etastasis), w hereas tPA is likely to play an im p o rtan t role in the con tro l o f intravascular fibrin degradation . T h e system includes specific p lasm inogen activator in h ib i tors (PAIs) w hich coun terac t the activity o f PAs, thereby restricting th e generation o f p lasm in for extracellular m atrix (E C M ) as well as for intravascular fib rin degradation .
