Role of Urokinase Plasminogen Activator System in the Invasiveness of Human Breast Cancer / 复旦学报（医学版）

ABSTRACT

Purpose　To investigate the role of urokinase plasminogen activator (uPA),uPA receptor (uPAR),tissue type plasminogen activator (tPA) and plasminogen activator inhibitor 1 (PAI-1) in the invasiveness of human breast cancer cells.　Methods　Three human breast cancer cell lines with different invasive ability were taken as research targets.RT-PCR and milk plates methods were used to detect the expression of uPA system members and the PA activities,respectively.Modified Boyden's chamber model was employed to detect the invasive ability of cancer cell.　Results　MDA-MB-231 could express high level of uPA,uPAR,PAI-1 and low level of tPA.MDA-MB-435 could express lower level of uPA and hight level of tPA,but no PAI-1 and uPAR were detected.MCF-7 could express lower level of uPAR and high level of PAI-1,but no uPA and tPA were detected.MDA-MB-231 cells showed the highest total PA and uPA activity.MDA-MB-435 cells also showed high total PA activity,but almost all the activity owed to tPA.MCF-7 showed almost no PA activity.Correlated with their PA activities,MDA-MB-231 was found the most invasive in vitro,followed by MDA-MB-435,and MCF-7 almost had no invasive ability.The antibodies against uPA and uPAR were significantly effective in reducing the matrigel invasiveness of MDA-MB-231 by approximately 83.1% and 43.9% respectively (P<0.05).　Conclusions　Co-expression of uPA,uPAR and PAI-1 in human breast cancer highly correlates with the invasiveness in vitro.