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

Abstract

Abstract Plasminogen activator inhibitor type 1 (PAI-1) is associated with tumour invasion, 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-1 on lung colonization by human HT-1080 fibrosarcoma cells. Full length PAI-1 cDNA was transfected in a non-aggressive HT-1080 clonal cell line (1–3C). Stable transfected clones were isolated of which one (3F52) secreted a 29-fold increase in PAI-1 protein levels (29.1±6.5 μg/10 6 cells/24 h) as compared with control mock transfected cells (1.0±0.2 μg/10 6 cells/24 h). 3F52 cells were significantly better able to form lung colonies after i.v. tail vein injection of athymic mice (mean number of colonies±SE 238±105) as compared with control cells (8±7). In addition, PAI-1 overexpressing cells were between 1.5 and 2.5 fold more adhesive to extracellular matrix membrane (ECM) proteins than mock transfected cells in an in vitro cell adhesion assay. These findings provide experimental support that PAI-1 facilitates tumour cell lodgement in vivo and adhesion of HT-1080 cells in vitro.