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AN INHIBITOR OF PLASMINOGEN ACTIVATOR PRODUCED BY TUMOUR CELL FUSION HYBRIDS
Author(s) -
BadenochJones Peter,
Ramshaw Ian A,
Grant Adrienne
Publication year - 1985
Publication title -
australian journal of experimental biology and medical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0004-945X
DOI - 10.1038/icb.1985.40
Subject(s) - plasmin , cycloheximide , trypsin , cell culture , plasminogen activator , urokinase , microbiology and biotechnology , trypsin inhibitor , chemistry , polyacrylamide gel electrophoresis , biology , biochemistry , enzyme , endocrinology , protein biosynthesis , genetics
Summary Expression of plasminogen activator (PA) activity may be an important factor in the ability of tumour cells to metastasize; however, not all metastatic cells product detectable PA activity. Conditioned culture media from revertant metastatic clones of cells derived by fusion of metastatic and non‐metastatic rat mammary adenocarcinoma cells were found to contain a potent inhibitor of PA. This inhibited thrombin, human urokinase (UK) and tumour‐derived PA, but not plasmin or trypsin. Inhibition was still obtained after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate (SDS‐PAGE) of mixtures of PA and inhibitor, followed by development of PA activity on fibrin overlays. The PA inhibitor eluted from Sephadex G‐200 over a broad M.wt. range (35,000‐80,000) and was inactivated by heating to 70° for 30 min. The appearance of inhibitory activity in the culture media was time‐dependent and could be reduced by incubation of cells with cycloheximide. Because of these findings, the possible presence of inhibitors should be considered in investigations into the role of PA in the metastatic process.