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) activity was purified from the extracts of extracellular matrix of highly 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 followed by reversed phase separation in a high performance liquid chromatography system. The purified protein in the immobilized conditions enhanced u-PA activity in both plasminogen activation and S-2444 amidolysis by 4.6- and 2.8-fold increases in the second order rate constants (Kcat/K(m)), respectively. This protein was related to neither plasminogen nor single-chain u-PA by the immunological studies and with respect to retention time on reversed phase analysis. These results suggest that the purified material acts as an enhancer of u-PA in extracellular matrix of the cancer cells, inducing an effective tissue destruction and cell invasion and possessing a highly metastatic potential.
Hagiya
Y
Y
Department of Physiology, Kinki University School of Medicine, Osakasayama City, Japan.
Fukao
H
H
Ueshima
S
S
Okada
K
K
Inufusa
H
H
Kamiishi
H
H
Matsuo
O
O
D000230:Adenocarcinoma / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D002845:Chromatography; D004586:Electrophoresis; D016326:Extracellular Matrix Proteins / Q000302:isolation & purification* / Q000378:metabolism / Q000494:pharmacology; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D008175:Lung Neoplasms / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D013268:Stimulation, Chemical; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects* / Q000378:metabolism*
D016326:Extracellular Matrix Proteins; D009363:Neoplasm Proteins; D014568:Urokinase-Type Plasminogen Activator