INFLUENCE OF 12(S)-HYDROXYEICOSATETRAENOIC ACID (12(S)-HETE) ON THE LOCALIZATION OF CATHEPSIN-B AND CATHEPSIN-L IN HUMAN LUNG-TUMOR CELLS

Cathepsins B and L are catabolic lysosomal enzymes but are likely cand idates for extracellular proteolysis in normal and malignant processes , The signal mediator 12(S)-HETE selectively triggers a shot-gun relea se of cathepsin B. We have therefore investigated the intracellular di stribution of cathepsins in unstimulated and 12(S)-HETE-stimulated tum or cells, Cathepsins B and L have only limited colocalization, which i s found in the regions of synthesis and sorting (endoplasmic reticulum , Golgi, trans Golgi network), Treatment by 12(S)-HETE scatters cathep sin B but not cathepsin L and preform of cathepsin B, Colocalization w ith both mannose 6-phosphate receptors is very limited for both cathep sins. But extensive colocalization of cathepsin B and the endosomal/ly sosomal marker CD63 (LIMP-I) documents the main fraction of the enzyme in these compartments, The supposed non-lysosomal fraction of catheps in B is very likely the secretable material which follows a regulated secretory pathway, Storage and regulated secretion in tumor cells supp ort extracellular proteolysis as a means in invasion which may lead to metastasis, But the mechanisms by which cells might acquire and event ually apply this means is still unknown.