RETINOIC ACID INHIBITION OF A TUMOR PROTEASE IMMOBILIZED ON CELL-SURFACES AND IN FREE SOLUTION

Retinoids are inhibitors of tumour cell proliferation in culture and h ave been shown to suppress carcinogenesis and decrease the levels of p roteases. The present study has demonstrated that retinoic acid is a p otential non-competitive inhibitor of a protease (GB) immobilised on t he surfaces of tumour cells in thin sections and free GB in solution. The enzymic status of GB on the cell surfaces in sections has been det ermined by challenging the retinoic acid-treated cells with a second f luorescent inhibitor (9-AA), followed by fluorescence microscopic anal ysis. The inhibition of cell surface GB by retinoic acid was demonstra ted to be reversible. The activity of soluble GB has been measured by the MUGB assay in the presence and absence of retinoic acid. It is sug gested that retinoic acid acts on GB by interacting with a binding sit e, different from the active site, and causes major conformational cha nges, resulting in enzyme inhibition. It is possible that the modulati on of OB activity by retinoic acid may play a role in the control of c ell migration and metastasis.