COEXPRESSION OF UROKINASE-TYPE PLASMINOGEN-ACTIVATOR AND ITS RECEPTORIN HUMAN GASTRIC-CANCER CELL-LINES CORRELATES WITH THEIR INVASIVENESSAND TUMORIGENICITY

The expression of urokinase-type plasminogen activator (u-PA), its rec eptor (u-PAR) and metalloproteases activity were analyzed in 4 human g astric-cancer cell lines (AGS, Hs746T, SNU-1, and SNU-5), in an attemp t to relate these activities to their invasive potential acid tumorige nicity on the modified chorioallantoic membranes (CAM) of chick embryo s, Only I of the 4 cell lines tested, Hs746T, expressed both u-PA and u-PAR as well as MMP-2, but not MMP-9. This cell line was both tumorig enic and highly invasive (51.3 +/- 13.1%) on a modified CAM, Its invas ive capacity was comparable with that of a highly malignant human epid ermoid-carcinoma cell line (HEp3), which usually showed 40 to 50% inva siveness, The 3 other cell lines all produced MMP-2 and MMP-9, but onl y AGS showed moderate invasiveness (24.2 +/- 8.8%). While antibodies t o u-PA were significantly effective in reducing CAM invasiveness of Hs 746T cells by approximately 40%, the invasiveness of the t-PA-expressi ng ACS cell line was not affected by anti-t-PA antibodies, These resul ts suggest that when one of the components of the u-PA/u-PAR system (t he enzyme and/or the receptor) is not produced and u-PA/u-PAR-dependen t cell-surface proteolytic activity is thereby diminished, the maligna nt phenotype that can be determined by tumorigenicity and invasion of connective tissue on a CAM is compromised. Production of both type-IV collagenases (MMP-2 and MMP-9) cannot offset this deficiency. (C) 1997 Wiley-Liss, Inc.