IN-VITRO ANTIPROLIFERATIVE AND ANTI-INVASIVE ROLE OF AMINO-TERMINAL FRAGMENT OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR ON 8701-BC BREAST-CANCER CELLS

8701-BC cells, derived from a primary carcinoma of the breast, constit utively express mRNA for urokinase-type plasminogen activator (uPA). I n this paper, we demonstrated the presence of uPA in the conditioned m edium, and of uPA-receptor (uPAR) on the cell surface of 8701-BC cells , which therefore have the potential for an autocrine mechanism of uPA -mediated stimulation. We examined whether exogenous addition of eithe r intact uPA, or its amino-terminal fragment (uPA-ATF), which lacks ca talytic activity but retains the uPAR binding site and a growth factor -like domain, or immunoneutralisation of endogenous uPA-uPAR interacti ons could exert any effect on the proliferative and invasive behaviour of 8701-BC cells. The data demonstrate that, while uPA promotes growt h and invasion of 8701-BC cells, its effect reversed by blocking uPA-u PAR interactions, uPA-ATF not only fails to impart growth factor-like signals, but also restrains cell invasion in vitro. In the light of th ese and other data, an active participation of ATF in the complex cell -ECM network of interactions underlying cancer progression can be post ulated. In addition, it appears worth considering the possibility of t esting the effect of this uPA fragment in vivo for the therapy of brea st (and possibly other) human invasive carcinomas. (C) 1996 Elsevier S cience Ltd