Inhibitors of guanidinobenzoatase and their possible role in cell migration.

Guanidinobenzoatase is a cell surface protease associated with cells capable of migration, this enzyme is trypsin-like and cleaves the link peptide Gly-Arg-Gly-Asp of fibronectin. A fluorescent probe, 9-aminoacridine, has been used to locate cells possessing guanidinobenzoatase by fluorescent microscopy. 9-aminoacridine is a competitive inhibitor of this enzyme and does not react with the cell-bound enzyme when the latter is already inhibited by a tissue-specific protein inhibitor of guanidino-benzoatase. We have employed sections of normal and tumour-bearing tissues as a test system to demonstrate the presence of tissue-specific inhibitors of guanidinobenzoatase and to exchange inhibitors on the cell-bound guanidinobenzoatase. The activity of the enzyme in vivo is suppressed by the presence of inhibitors; the latter may be displaced by oxidative disulphide-exchange reactions resulting in regain of enzymic activity on the cell surface. We believe these inhibitors may control cell migration in vivo and therefore believe their study is important in gaining an understanding of the regulation of metastasis.