title: Carboxypeptidases cathepsins X and B display distinct protein profile in human cells and tissues.
abstract: Cathepsin X, a recently discovered lysosomal cysteine protease, shares common structural features and activity properties with cysteine protease cathepsin B. Based on its widespread mRNA distribution in primary tumors and tumor cell lines, a redundant function in tumor progression has been proposed. In this study, we have shown that these two related proteases exhibit different profiles with respect to their protein distribution in cells and tissues and to their possible roles in malignancy. Protein level of cathepsin X did not differ significantly between matched pairs of lung tumor and adjacent lung tissue obtained from patients with lung cancer whereas that of cathepsin B was 9.6-fold higher in tumor compared to adjacent lung tissue. Immunohistochemical analysis of lung tumor cathepsin X revealed very faint staining in tumor cells but positive staining in infiltrated histiocytes, alveolar macrophages, bronchial epithelial cells, and alveolar type II cells. Cathepsin X stained positive also in CD68+ cells in germinal centers of secondary follicles in lymph nodes, corresponding to tingible body macrophages. Two cell lines with proven invasive behavior, MCF-10A neoT and MDA-MB 231, showed positive staining for cathepsin B, but negative for cathepsin X. We showed that the invasive potential of MCF-10A neoT cells can be impaired by specific inhibitor of cathepsin B but not by that of cathepsin X. Cathepsin X was found in large amounts in the pro-monocytic U-937 cell line, in monocytes and in dendritic cells, generated from monocytes in vitro. Our results show that cathepsin X is not involved in degradation of extracellular matrix, a proteolytic event leading to tumor cell invasion and metastasis. Its expression, restricted to immune cells suggests a role in phagocytosis and the regulation of immune response.
authors.affiliation: Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia.
authors.forename: Janko
authors.initials: J
authors.lastname: Kos
authors.forename: Andreja
authors.initials: A
authors.lastname: Sekirnik
authors.forename: Ales
authors.initials: A
authors.lastname: Premzl
authors.forename: Valentina
authors.initials: V
authors.lastname: Zavasnik Bergant
authors.forename: Tomaz
authors.initials: T
authors.lastname: Langerholc
authors.forename: Boris
authors.initials: B
authors.lastname: Turk
authors.forename: Bernd
authors.initials: B
authors.lastname: Werle
authors.forename: Rastko
authors.initials: R
authors.lastname: Golouh
authors.forename: Urska
authors.initials: U
authors.lastname: Repnik
authors.forename: Matjaz
authors.initials: M
authors.lastname: Jeras
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000918:Antibody Specificity / Q000276:immunology; D002268:Carboxypeptidases / Q000032:analysis* / Q000276:immunology; D002401:Cathepsin B / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D056657:Cathepsin K; D002403:Cathepsins / Q000032:analysis* / Q000276:immunology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003094:Collagen; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003600:Cytosol / Q000737:chemistry / Q000201:enzymology; D003713:Dendritic Cells / Q000737:chemistry / Q000201:enzymology; D004338:Drug Combinations; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008168:Lung / Q000737:chemistry / Q000201:enzymology; D008175:Lung Neoplasms / Q000737:chemistry / Q000201:enzymology / Q000473:pathology; D008198:Lymph Nodes / Q000737:chemistry / Q000201:enzymology; D009000:Monocytes / Q000737:chemistry / Q000201:enzymology; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D020298:U937 Cells
chemical_list: D000911:Antibodies, Monoclonal; D015853:Cysteine Proteinase Inhibitors; D004338:Drug Combinations; D007797:Laminin; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D002268:Carboxypeptidases; D002403:Cathepsins; D002401:Cathepsin B; C534130:CTSK protein, human; D056657:Cathepsin K; D007930:Leucine; C024974:E 64