EXPRESSION AND RELEASE OF PLASMINOGEN ACTIVATORS, THEIR INHIBITORS AND RECEPTOR BY HUMAN TUMOR-CELL LINES

Plasminogen activators (PAs) and their inhibitors (PAIs) can be produc ed by tumor cells and surrounding inflammatory cells and fibroblasts. The present study evaluate both the expression and release of PAs (uPA and tPA) and PAIs (PAI-1 and PAI-2) from cultured cells, and also the expression of uPA receptor (uPAR). immunocytochemistry showed that PA s, PAIs and uPAR were present to different extents on the surface of c olon carcinoma cells (Caco-2, HT-29), malignant melanoma cells (LOX) a nd normal fibroblasts, uPA immunoreactivity was intermediate in Caco-2 , HT-29 and LOX and weak in the fibroblasts. tPA immunoreactivity was inter-mediate in Caco-2 and LOX and weak in HT-29 and fibroblasts. PAI -1 and PAI-2 immunoreactivities were absent in NT-29, weak in Caco-2 a nd strong in fibroblasts. In LOX the immunoreactivity was intermediate for PAI-1 and strong for PAI-2. uPAR immunoreactivity was weak in Cac o-2, HT-29 and LOX and negative in fibroblasts. ELISAs on conditioned medium detected that the colon carcinoma cells Caco-2 and HT-29 diet n ot release any PAs oi PAIs. LOX released tPA (median 9 ng/million cell s at 72 hours), PAI-1 (1050 ng/million cells) and PAI-2 (245 ng/millio n cells), and fibroblasts released uPA (1 ng/million cells) and PAI-1 (910 ng/million cells). These results shaw that both tumor cells and f ibroblasts express tissue desctructive enzymes, PAs and PAIs, whereas only the tumor cells express the uPAR required for focalization and re gulation of PA activity at the cell surface. The melanoma cells LOX an d fibroblasts also released PAs and PAIs, in contrast to the colon car cinoma cells Caco-2 and HT-29.