ENHANCED UROKINASE-TYPE PLASMINOGEN-ACTIVATOR ACTIVITY BY EXTRACELLULAR-MATRIX PROTEIN OBTAINED FROM HIGHLY METASTATIC HUMAN LUNG ADENOCARCINOMA CELL-LINE

A protein which enhanced urokinase-type plasminogen activator (u-PA) a ctivity was purified from the extracts of extracellular matrix of high ly metastatic cell line HAL-8 derived from human lung adenocarcinoma. The protein showed a single band with molecular weight of 65 kDa after the purification by Sephadex G-150 and diethylaminoethyl-cellulose fo llowed by reversed phase separation in a high performance liquid chrom atography system. The purified protein in the immobilized conditions e nhanced u-PA activity in both plasminogen activation and S-2444 amidol ysis by 4.6- and 2.8-fold increases in the Second order rate constants (k(cat)/K-m), respectively, This protein was related to neither plasm inogen nor single-chain u-PA by the immunological studies and with res pect to retention time on reversed phase analysis. These results sugge st that the purified material acts as an enhancer of u-PA in extracell ular matrix of the cancer cells, inducing an effective tissue destruct ion and cell invasion and possessing a highly metastatic potential.