Thrombospondin and transforming growth factor-beta 1 increase expression of urokinase-type plasminogen activator and plasminogen activator inhibitor-1 in human MDA-MB-231 breast cancer cells

摘要: Background. Thrombospondin is a high molecular weight adhesive glycoprotein that has been shown to function in mechanisms of tumor progression. The authors' previous studies have thrombospondin promotes human lung carcinoma invasion by up-regulation the plasminogen activator system through mechanism involving activation transforming growth factor-beta 1 (TGF-beta 1). In this study, similar throm-bospondin-mediated operative breast cells described. Methods. effect and TGF-beta on capacity line activate was measured as well physiologic consequences these activities cell adhesion proliferation. Plasminogen assessed measuring plasmin activity inhibitor-1 (PAI-1) levels cell-conditioned media cell-associated urokinase-type (uPA) levels. Results. Treatment MDA-MB-231 with either or caused increased secretion PAI-1 concomitant decrease activity, whereas uPA expression respect controls. (40 μMg/ml) (5 ng/ml) stimulated secrete 5.5- 6.7-fold more than controls, respectively, decreased culture medium. Conversely, μg/ml) express 4.55- 5.38-fold respectively. induced flattened spread appearance no These effects could be reversed antibodies were not due contamination active 1. Conclusions. similarly increase cell-secreted PAI-1. data suggest may only an molecule, but 1, modulate surface protease expression. addition, observations promote metastasis increasing uPA-mediated invasion, action PAI-1, also protect blood-born emboli from destruction host fibrinolytic enzymes. Cancer 1995;76:998–1005.