Expression, subcellular distribution and plasma membrane binding of cathepsin B and gelatinases in bone metastatic tissue.
The possible application of proteinase inhibitors in the support of anti-tumor chemotherapy requires profound knowledge of the proteinases involved in malignant processes. Therefore, the occurrence of cathepsins B, D, H, L and S and of gelatinases, urokinase plasminogen activator and stromelysins was studied in biopsies of aggressive human bone metastases, of low invading basal cell carcinomas, and in normal placenta as control, by activity measurements and zymographic techniques. Cathepsin B and L, as well as gelatinase B, were shown to be overexpressed in bone metastases, suggesting a function during the metastatic process. Subcellular fractionation allowed detection of differential sorting of cathepsin B and gelatinases in metastatic tissue and also in normal human placenta. Plasma membrane binding could be demonstrated for both cathepsin B and gelatinase B. Whereas cathepsin B is at least partially bound to plasma membranes via alpha 2-macroglobulin and its LRP/alpha 2-macroglobulin receptor, gelatinase B binds to plasma membranes by an unknown mechanism.
Arkona
C
C
Institute of Biochemistry, Medical Faculty, Friedrich-Schiller-University, Jena, Germany.
Wiederanders
B
B
D019870:1-Phosphatidylinositol 4-Kinase; D015720:5'-Nucleotidase / Q000378:metabolism; D000135:Acid Phosphatase / Q000378:metabolism; D001859:Bone Neoplasms / Q000201:enzymology / Q000556:secondary*; D002401:Cathepsin B / Q000378:metabolism*; D056668:Cathepsin L; D002403:Cathepsins / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D017364:Collagenases / Q000378:metabolism; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020780:Matrix Metalloproteinase 9; D009362:Neoplasm Metastasis; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism; D013347:Subcellular Fractions / Q000201:enzymology; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D007770:L-Lactate Dehydrogenase; D017853:Phosphotransferases (Alcohol Group Acceptor); D019870:1-Phosphatidylinositol 4-Kinase; D000135:Acid Phosphatase; D015720:5'-Nucleotidase; D001619:beta-N-Acetylhexosaminidases; D002403:Cathepsins; D010450:Endopeptidases; D014568:Urokinase-Type Plasminogen Activator; D003546:Cysteine Endopeptidases; D002401:Cathepsin B; C534281:CTSL protein, human; D056668:Cathepsin L; D017364:Collagenases; D018093:Gelatinases; D020780:Matrix Metalloproteinase 9