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 unknown.
Ulbricht
B
B
Deutsches Krebsforschungszentrum, Heidelberg/Germany.
Henny
H
H
Horstmann
H
H
Spring
H
H
Faigle
W
W
Spiess
E
E
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000494:pharmacology*; D015703:Antigens, CD / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism*; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms; D008247:Lysosomes / Q000378:metabolism; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D060149:Tetraspanin 30; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C554586:CD63 protein, human; D010980:Platelet Membrane Glycoproteins; D011498:Protein Precursors; D017527:Receptor, IGF Type 2; D060149:Tetraspanin 30; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L