Abstract
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Up-regulation of the urokinase plasminogen activation (uPA) system leads to increased
cancer invasion and metastasis. Plasminogen activator inhibitors type-1 (PAI-1/SERPINE1)
and type-2 (PAI-2/SERPINB2) have similar uPA inhibitory properties yet PAI-1 promotes
cell invasion by modulating cell adhesion and migration. High tumour PAI-2 levels are
associated with improved prognoses. Herein we show that PAI-2 is capable of inhibiting
uPA in the presence of PAI-1, particularly on adherent cells in the presence of vitronectin.
This suggests that elevated levels of PAI-2 in the tumour microenvironment could outcompete
PAI-1 for uPA inhibition through its inhibitory serpin function. However, PAI-1 modulated
cell adhesion in a largely uPA-independent manner consequently PAI-2 could not
counteract the effects of PAI-1 on adhesion/migration. Thus studies aimed at further characterising
the interplay between PAI-1 and PAI-2 on uPA-dependent pro-invasive processes
are warranted.