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 candidates for extracellular proteolysis in normal and malignant processes. The signal mediator 12(S)−HETE selectively triggers a shot−gun release of cathepsin B. We have therefore investigated the intracellular distribution of cathepsins in unstimulated and 12(S)−HETE−stimulated tumor cells. Cathepsins B and L have only limited colocalization, which is found in the regions of synthesis and sorting (endoplasmic reticulum, Golgi, trans Golgi network). Treatment by 12(S)−HETE scatters cathepsin B but not cathepsin L and proform of cathepsin B. Colocalization with both mannose 6−phosphate receptors is very limited for both cathepsins. But extensive colocalization of cathepsin B and the endosomal/lysosomal marker CD63 (LIMP−I) documents the main fraction of the enzyme in these compartments. The supposed non−lysosomal fraction of cathepsin B is very likely the secretable material which follows a regulated secretory pathway. Storage and regulated secretion in tumor cells support extracellular proteolysis as a means in invasion which may lead to metastasis. But the mechanisms by which cells might acquire and eventually apply this means is still unknow