A CLEAVED FORM OF THE RECEPTOR FOR UROKINASE-TYPE PLASMINOGEN-ACTIVATOR IN INVASIVE TRANSPLANTED HUMAN AND MURINE TUMORS

It was recently found that urokinase-type plasminogen activator (uPA) is involved in the cleavage of its receptor's 3 domains (the ligand bi nding domain 1) and leaving the 2 others [uPAR(2 + 3)] anchored to the cell surface. With monoclonal antibodies (MAbs) we have now identifie d human uPAR(2 + 3) in lysates of invasive human MDA-MB-231 mammary ca rcinomas xenografted into nude mice. The production of peptide antibod ies recognizing different domains of murine uPAR made it possible to i dentify a similar cleaved form of uPAR, murine uPAR(2 + 3), in extract s of primary Lewis lung carcinomas. Cleavage of uPAR also occurs in cu ltured MDA-MB-231 cells and Lewis lung carcinoma cells. This cleavage is inhibited by anticatalytic antibodies to either human or murine uPA , respectively, indicating that it is catalyzed by either uPA or plasm a generated by uPA. The mount of uPAR(2 + 3) may therefore be directly related to the activity of the uPA system and it is possible that the level of uPAR(2 + 3) in cancer tissue may prove to be a stronger prog nostic parameter than the levels of either full-length uPAR or UPA. (C ) 1994 Wiley-Liss, Inc.