Responses

Extract

The urokinase-type plasminogen activator receptor (uPAR) focuses urokinase-type PA (uPA) proteolytic activity at the cell surface to facilitate tumor invasion. Our work ( 1 ) suggested that in vitro invasion of extracellular matrix by bladder cancer cells requires both a source of uPA and its receptor. Two additional studies ( 2 , 3 ) support this hypothesis. In a study of four human gastric cancer cell lines, the cell line expressing both uPA and its receptor (IIs746T) showed the highest invasive potential on modified chorioallantoic membranes (CAMs) of chick embryos. T-Lymphoblastic leukemia cells able to transmigrate through an extracellular matrix barrier were observed to express uPA and high levels of uPAR ( 3 ). Inhibition of uPA/uPAR interaction reduced the invasive potential of tumor cells in vitro in all three studies. An additional recent observation ( 4 ) showed that clones of Hep3 cells transfected with a vector expressing uPAR antisense RNA reduced cell surface uPAR levels. Low cell-surface uPAR expression was associated directly with significantly reduced invasiveness on CAMs of chick embryos, and cells appeared dormant for up to 5 months. Thus, a synergistic action between two components of the PA system appears to enhance invasion in laboratory studies. Inhibition of invasion and tumorgenicity can be affect through alteration of the uPA/uPAR interaction.