Overexpression of plasminogen activator inhibitor type-1 in HT-1080 fibrosarcoma cells promotes lung colonisation and in vitro cell adhesion

Plasminogen activator inhibitor type 1 (PAI-1) is associated with tumour in vasion, angiogenesis and metastatic spread. it is also a strong prognostic factor for relapse in a number of human cancers. This study was designed to investigate the effects of overexpression of PAI-I on lung colonization by human HT-1080 fibrosarcoma cells. Full length PAI-1 cDNA was transfected i n a non-aggressive MT-1080 clonal cell line (1-3C). Stable transfected clon es were isolated of which one (3F52) secreted a 29-fold increase in PAI-1 p rotein levels (29.1+/-6.5 mu g/10(6) cells/24 h) as compared with control m ock transfected cells (1.0+/-0.2 mu g/10(6) cells/24 h). 3F52 cells were si gnificantly better able to form lung colonies after i.v. tail vein injectio n of athymic mice (mean number of colonies+/-SE 238+/-105) as compared with control cells (8+/-7). In addition, PAI-1 overexpressing cells were betwee n 1.5 and 2.5 fold more adhesive to extracellular matrix membrane (ECM) pro teins than mock transfected cells in an in vitro cell adhesion assay. These findings provide experimental support that PAI-1 facilitates tumour cell l odgement in vivo and adhesion of MT-1080 cells in vitro. (C) 2000 Harcourt Publishers Ltd.