Author/Editor     Kos, Janko; Sekirnik, Andreja; Premzl, Aleš; Zavašnik-Bergant, Valentina; Langerholc, Tomaž; Repnik, Urška; Turk, Boris; Werle, Bernd; Golouh, Rastko; Jeras, Matjaž; Turk, Vito
Title     Carboxypeptidases cathepsins X and B display distinct protein profile in human cells and tissues
Type     članek
Source     Exp Cell Res
Vol. and No.     Letnik 306, št. 1
Publication year     2005
Volume     str. 103-13
Language     eng
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 riot 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 speciiic 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 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.
Descriptors     CARBOXYPEPTIDASES
CATHEPSIN B
CATHEPSINS
CYSTEINE PROTEINASE INHIBITORS
DENDRITIC CELLS
ANTIBODIES, MONOCLONAL
ANTIBODY SPECIFICITY
TUMOR CELLS, CULTURED
CELL MOVEMENT
COLLAGEN
CYTOSOL
DRUG COMBINATIONS
FLOW CYTOMETRY
LEUCINE
LUNG
LUNG NEOPLASMS
LYMPH NODES
MONOCYTES
NEOPLASM INVASIVENESS
PROTEOGLYCANS