EFFECTS OF URINARY TRYPSIN-INHIBITOR ON THE INVASION OF RECONSTITUTEDBASEMENT-MEMBRANES BY OVARIAN-CANCER CELLS

Using the human ovarian cancer cell line HOC-1, we investigated the ef fects of urinary trypsin inhibitor (UTI) purified from human urine and its related synthetic peptides on the invasive potential of cancer ce lls in an in vitro assay. Invasiveness of tumor cells was determined u sing a modified Boyden chamber and a reconstituted basement membrane M atrigel. Three peptides (peptide 1, peptide 2, and peptide 3), represe nting sequences within UTI, were synthesized. HOC-1 cells showed detec table and reproducible levels of expression of surface urokinase-type plasminogen activator (uPA) and plasminogen/plasmin by cell ELISAs and enzyme assays. UTI was found to strongly inhibit plasmin and human le ukocyte elastase (HLE). Peptide 2 and peptide 3 specifically inhibit H LE and plasmin activity respectively. Peptide 1 has essentially no inh ibitory activity. Treatment with UTI and peptide 3 reduces the inciden ce of invasion, whereas peptide 1 and peptide 2 do not affect invasion . The inhibitory effect on cell invasion is dose-dependent. The proteo lytic enzyme plasmin may be involved in human ovarian cancer invasion in extracellular matrix degradation, and the use of UTI and peptide 3 that inhibits plasmin specifically reduces invasion by tumor cells. (C ) 1994 Wiley-Liss, Inc.