cathepsin-g and Lung-Neoplasms

To investigate novel potential biomarkers for antidiastole of tuberculous pleural effusion (TPE) from malignant pleural effusion (MPE).. iTRAQTM-coupled LC-MS/MS were applied to analyze the proteome of TPE and MPE samples. The candidate proteins were verified by enzyme-linked immunosorbent assay.. A total of 432 differential proteins were identified. Enzyme-linked immunosorbent assay revealed significantly higher levels of fibronectin (FN) and cathepsin G (CTSG) in MPE than in TPE, but lower levels of leukotriene-A4 hydrolase (LTA4H). The receiver operator characteristic values were 0.285 for FN, 0.64 for LTA4H, 0.337 for CTSG and 0.793 for a combination of these candidate markers.. FN, LTA4H and CTSG were identified as potential biomarkers to differentiate TPE from MPE and their combination exhibited higher diagnostic capacity.

Topics: Adult; Biomarkers; Carcinoma, Non-Small-Cell Lung; Cathepsin G; Diagnosis, Differential; Epoxide Hydrolases; Female; Fibronectins; Follow-Up Studies; Humans; Lung Neoplasms; Male; Middle Aged; Pleural Effusion, Malignant; Proteome; ROC Curve; Tuberculosis, Pleural

To investigate the changes in serum protease and cytokine in patients with silicosis, tuberculosis, and lung cancer.. Serum samples of patients with silicosis, tuberculosis, and lung cancer were collected. The variation trends of the expression of granzyme A, cathepsin G, apolipoprotein A, and interferon-β (IFN-β) were analyzed using enzyme-linked immunosorbent assay.. The concentration of apolipoprotein A of the silicosis group was 200 µg/ml, significantly higher than those of the tuberculosis and lung cancer groups (P < 0.05), and the lung cancer group had a significantly higher concentration of apolipoprotein A compared with the tuberculosis group (P < 0.05). The silicosis group had significantly higher expression of cathepsin G compared with the tuberculosis and lung cancer groups (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in the concentration of cathepsin G (P > 0.05). The tuberculosis group had a significantly higher concentration of granzyme A than the silicosis and lung cancer groups (P < 0.05), and the silicosis group and lung cancer group had similar protein concentration trends (P > 0.05). The tuberculosis group and lung cancer group had significantly higher concentration of IFN-β compared with the silicosis group (P < 0.05), and the tuberculosis group and lung cancer group showed no significant difference in IFN-β concentration (P > 0.05).. This study may offer diagnostic markers for the clinical diagnosis of silicosis, tuberculosis, and lung cancer, and could provide a basis for the research, as well as potential molecular targets for the diagnosis and treatment of these diseases.

Topics: Biomarkers; Cathepsin G; Cytokines; Endopeptidases; Enzyme-Linked Immunosorbent Assay; Granzymes; Humans; Interferon-beta; Lung Neoplasms; Silicosis; Tuberculosis

Inflammation is inextricably associated with primary tumor progression. However, the contribution of inflammation to tumor outgrowth in metastatic organs has remained underexplored. Here, we show that extrinsic inflammation in the lungs leads to the recruitment of bone marrow-derived neutrophils, which degranulate azurophilic granules to release the Ser proteases, elastase and cathepsin G, resulting in the proteolytic destruction of the antitumorigenic factor thrombospondin-1 (Tsp-1). Genetic ablation of these neutrophil proteases protected Tsp-1 from degradation and suppressed lung metastasis. These results provide mechanistic insights into the contribution of inflammatory neutrophils to metastasis and highlight the unique neutrophil protease-Tsp-1 axis as a potential antimetastatic therapeutic target.

Topics: Animals; Blotting, Western; Bone Marrow Transplantation; Cathepsin G; Cell Line, Tumor; Female; Flow Cytometry; Gene Expression; Leukocyte Elastase; Lipopolysaccharides; Lung Neoplasms; Mice, Inbred C57BL; Mice, Knockout; Neoplasms, Experimental; Neutrophils; Peptide Hydrolases; Pneumonia; Proteolysis; Reverse Transcriptase Polymerase Chain Reaction; Serine Proteases; Thrombospondin 1

Neutrophil elastase (NE) is a neutrophil-derived serine proteinase with broad substrate specificity. We have recently demonstrated that NE is capable of entering tumor cell endosomes and processing novel intracellular substrates. In the current study, we sought to determine the mechanism by which NE enters tumor cells. Our results show that NE enters into early endosomal antigen-1(+) endosomes in a dynamin- and clathrin-dependent but flotillin-1- and caveolin-1-independent fashion. Cathepsin G (but not proteinase-3) also enters tumor endosomes via the same mechanism. We utilized (125)I-labeled NE to demonstrate that NE binds to the surface of cancer cells. Incubation of radiolabeled NE with lung cancer cells displays a dissociation constant (K(d)) of 284 nm. Because NE is known to bind to heparan sulfate- and chondroitin sulfate-containing proteoglycans, we treated cells with glycanases to remove these confounding factors, which did not significantly diminish cell surface binding or endosomal entry. Thus, NE and CG bind to the surface of cancer cells, presumably to a cell surface receptor, and subsequently undergo clathrin pit-mediated endocytosis.

Topics: Animals; Cathepsin G; Caveolin 1; CHO Cells; Chondroitin Sulfates; Clathrin; Coated Pits, Cell-Membrane; Cricetinae; Cricetulus; Endocytosis; Humans; Leukocyte Elastase; Lung Neoplasms; Neoplasm Proteins; Protein Binding; Protein Transport

Activity and tissue localization of cathepsin G were examined in tumors deriving from 73 patients with non small cell lung cancer. Activity of cathepsin G was highest in adenocarcinoma, lower in planoepitheliale cancer, the lowest in macrocellular cancer. In all histological types of tumors cathepsin G activity in supernatants was lower than in sediments. The enzyme immunohistochemically was localized in neutrophils. There is evident correlation between neutrophil numbers and cathepsin G activity in examined cancer types. Result of our examinations indicate a relationship between cathepsin G activity, grade of tumor differentiation and particular clinical stages of disease.

Topics: Adenocarcinoma; Adult; Aged; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cathepsin G; Cathepsins; Cell Differentiation; Cell Fractionation; Female; Humans; Lung; Lung Neoplasms; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Proteins; Neoplasm Staging; Neutrophils; Serine Endopeptidases; Solubility