Journal of Cell Science, Vol 36, Issue 1 241-252, Copyright © 1979 by Company of Biologists

JOURNAL ARTICLES

Cell-associated proteases affect tumour cell migration in vitro

J Varani, W Orr and PA Ward

The in vitro migratory activity of mouse fibrosarcoma cells in medium containing either foetal calf serum or normal human serum was studied. These 2 sera were studied because foetal calf serum contains high levels of protease inhibitor activity while human serum contains much less. The cells migrated actively in medium with foetal calf serum but migration was greatly inhibited in human serum-containing medium. When protease inhibitors such as soybean trypsin inhibitor, lima bean trypsin inhibitor and bovine pancreas trypsin inhibitor were added to human serum-containing medium cell migration was supported almost as effectively as in medium with foetal calf serum. Addition of epsilon-amino-n-caproic acid to human serum or depletion of the plasminogen from human serum did not enable it to support enhanced migration. epsilon-amino-n-caproic acid actually inhibited migration. A variant cell population with elevated levels of caseinolytic activity and elevated levels of activity against the substrate n-acetyl-DL-phenylalanine-beta-naphthyl ester (a substrate specific for chymotrypsin-like enzymes) was isolated from the parent cells. When the variant cells were compared to the parent cells regarding migratory activity in foetal calf serum or human serum-containing medium, the variant cells showed much less activity. Only a few, widely scattered variant cells migrated in the human serum-containing medium. These data suggest that a cell-associated factor interferes with the migration of the cells in medium with human serum. This factor apparently is neutralized in medium sontaining human serum to which protease inhibitors with antitrypsin activity have been added.