Cathepsin B in infiltrated lymph nodes is of prognostic significance for patients with nonsmall cell lung carcinoma (original) (raw)
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British journal of cancer, 2001
Cysteine proteinase cathepsin S (Cat S) is expressed mainly in lymphatic tissues and has been characterised as a key enzyme in major histocompatibility complex class II (MHC-II) mediated antigen presentation. Cat S has been measured in tissue cytosols of lung parenchyma, lung tumours and lymph nodes and in sera of patients with lung tumours and of healthy controls, by specific enzyme-linked immunosorbent assay (ELISA). A difference in Cat S level was found between tumour and adjacent control tissue cytosols of 60 lung cancer patients (median 4.3 vs. 2.8 ng mg(-1) protein). In lymph nodes obtained from 24 patients of the same group, the level of Cat S was significantly higher than in tumours or lung parenchyma (P< 0.001). Additionally, significantly higher levels were found in non-infiltrated than in infiltrated lymph nodes (median 16.6 vs 7.5 ng mg(-1) protein). Patients with low levels of Cat S in tumours and lung parenchyma exhibited a significantly higher risk of death than th...
British journal of cancer, 1999
In order to evaluate the possible role of the proteolytic enzyme cathepsin B (cath B) in human non-small cell lung cancer (NSCLC) we examined cath B concentrations (cath B(C)) and activities (cath B(A)) in homogenates of 127 pairs of lung tumour tissues and corresponding non-tumourous lung parenchyma. Total cath B activity (cath B(AT)) and enzymatic activity of the fraction of cath B, which is stable and active at pH 7.5 (cath B(A7.5)) were determined by a fluorogenic assay using synthetic substrate Z-Arg-Arg-AMC. The immunostaining pattern of cath B was determined in 239 lung tumour tissue sections, showing the presence of the enzyme in tumour cells (cath B(T-I)) and in tumour-associated histiocytes (cath B(H-I)). The median levels of cath B(AT), cath B(A7.5) and cath B(C) were 5.6-, 3.2- and 9.1-fold higher (P < 0.001), respectively, in tumour tissue than in non-tumourous lung parenchyma. Out of 131 tissue sections from patients with squamous cell carcinoma (SCC), 59.5% immunos...
Multiple forms of cathepsin b in human lung cancer
International Journal of Cancer, 1995
In this study we have examined, by means of isoelectric focusing (IEF) in native polyacrylamide gel and contact-print fluorescence zymography, whether human lung carcinomas and the lung parenchyma contain different pools of multiple charge forms of the cysteine proteinase cathepsin B. The isoelectric point (pl) patterns of cathepsin B from lung carcinoma and matched lung were similar, particularly with regard to 2 major intermediate acidic enzyme pl forms designated as I and II (plapp of 5.10 and 4.93 in tumors, and 5.1 I and 4.94 in lungs. respectively). The slightly acidic cathepsin B pl forms (plapp 5.47-5.19) in squamous-cell lung carcinoma '(SQCLC) were significantly more numerous than such enzyme pl forms in lungs. The numbers of the highly acidic cathepsin B pl forms (plqp 4.82433) were significantly higher in SQCLC and lung adenocarcinoma (ACL) than in matched lung. The activity distribution percentage in the set of highly acidic cathepsin B pl forms was significantly higher in SQCLC and ACL than in matched lung. We also observed that cathepsin B from SQCLC and matched lung was fully recoverable by IEF from inhibition by leupeptin. Using the cysteine-proteinase-specific inactivator E-64, we revealed by IEF that some cathepsin B isoforms (charge forms) from SQCLC were more resistant to inactivation by this compound than the corresponding enzyme isoforms from lungs. After IEF, the enzyme isoforms apparently lost their resistance to E-64. Our results indicate that the pool of multiple charge forms of cathepsin B in SQCLC and ACL is different from that in the lung, and also that there may be an increased level of loose complexes between cathepsin B and some proteins or polypep-
Cathepsins D, B, and L in malignant human lung tissue
Clinical cancer research : an official journal of the American Association for Cancer Research, 1996
The levels of cathepsins in malignant and surrounding nonmalignant lung tissue were determined in 17 non-small cell lung cancer specimens. Cathepsin (Cat) D activity was assayed using hemoglobin, whereas Cat B and Cat L activities were assayed using fluorimetric substrates, benzoylcarbonyl-Ala-Arg-Arg-7-amino-4-methylcoumarine and benzoylcarbonyl-Phe-Arg-7-amino-4-methylcoumarine, respectively. Cat protein concentrations were determined using ELISAs. In malignant tissues, the activities of Cat B and Cat L were significantly higher than the activities in nonmalignant tissues (P < 0.0012 and P < 0.0003, respectively), whereas Cat D concentration was not. There was also a 5.6-fold increase in median Cat B protein (P < 0.054) and a 2.2-fold increase in Cat L protein (P < 0.069). By contrast, the aspartic proteinase, Cat D protein, was not significantly increased in tumors versus control lung tissues. Moderate but significant correlation (r = 0.5, P < 0.045) between Cat B ...
Journal of Cancer Research and Clinical Oncology, 1991
The activities of dipeptidyl peptidase IV (DPP-IV), prolyl endopeptidase (PE) and cathepsin B (CB) were investigated in primary human lung tumours and matched lung parenchyma, using continuous-rate fluorometric assays of the enzymes. Squamous-cell lung carcinomas showed significantly higher specific activities of all three enzymes studied. In lung adenocarcinomas only activities of PE and CB were increased significantly. In a limited number of primary human lung tumours of other histological types the activities of DPP-IV, PE and CB were also elevated. Mixing the matched homogenates of lung tumours and lung parenchyma gave additive activities for each enzyme studied. A significant correlation between tumour/lung ratios of specific activities of DPP-IV and CB was observed.
American Journal of Clinical Pathology, 2006
Lung bronchioloalveolar carcinomas (BACs) are noninvasive tumors showing lepidic growth and excellent prognosis, whereas all the other variants of adenocarcinoma are invasive tumors with a worse prognosis. The identification of minimal invasive foci in adenocarcinoma, therefore, is of prognostic relevance. A series of 68 pulmonary tumors, including 40 acinar/papillary adenocarcinomas, 18 adenocarcinomas of the mixed subtype, and 10 BACs was tested by immunohistochemical analysis for cathepsin K expression, a proteinase involved in bone and extracellular matrix remodeling. Cathepsin K was produced by epithelial tumor cells in most invasive adenocarcinomas and, interestingly, by macrophages and fibroblasts in the stroma of invasive adenocarcinomas but not of BACs (P < .001). Our findings suggest pathogenetic implications of cathepsin K in the mechanisms of tumor invasiveness in lung carcinoma; in addition, cathepsin K immunodetection may be a valuable adjunct in the correct classification of pulmonary adenocarcinomas, especially in small sclerosing BACs and mixed adenocarcinoma subtypes with minimal infiltrative growth.
Biological Chemistry Hoppe-Seyler, 1995
In a series of pairs of lung tumor tissue and non-tumor lung parenchyma from 50 patients, the activity of cathepsin L was measured with Z-Phe-Arg-AMC using the inhibitor CA-074 to delimitate from cathepsin B activity also present in the tissue extracts. Cathepsin B was assessed in the same samples with its specific substrate Z-Arg-Arg-AMC. It was found that in tumor tissue the median activities of cathepsin L and cathepsin B were increased 1.6-fold and 4.9-fold, respectively. The levels of activity of both enzymes did not correlate with TNM stages nor with cell differentiation of bronchial carcinomas. Cathepsin L activity was found to be insignificantly higher in adenocarcinoma compared to squamous cell carcinoma, while cathepsin B activity did not vary across the histologies. The activities of both enzymes were low in pulmonary carcinoids, which are known to be low-grade malignant neoplasms. The amount of cathepsin B activity exceeded by far that of cathepsin L activity as proven by measurement with Z-Phe-Arg-AMC in the presence of the inhibitor Z-Phe-Phe-CHN 2 : 95-98% of cathepsin B activity vs 2-5% of cathepsin L activity were determined. By SDS-PAGE separation and immunoblot analysis, it could be demonstrated that significant amount of cathepsin L is complexed with the cysteine proteinase inhibitor kininogen. This explains the rather low cathepsin L activity values in the tissue extracts.
British journal of cancer, 2000
In order to evaluate the role of cysteine peptidase cathepsin H (Cath H) in human lung cancer its protein levels were determined in 148 pairs of lung tumour tissue and adjacent non-tumourous lung parenchyma using the enzyme-linked immunosorbent assay technique. Additionally, Cath H levels were determined in sera of 171 patients with malignant tumours, 34 patients with benign lung diseases and 47 healthy controls. The median level of Cath H in tumour tissue was 0.64 times that in the corresponding lung parenchyma. Relating tumour levels with histological type we found higher Cath H levels in small-cell and adenocarcinomas and lower levels in squamous cell carcinoma, large-cell carcinoma and secondary tumours. A significant difference in Cath H level between lung tumour tissue and non-tumourous lung parenchyma was associated with the group of cigarette smokers (156 vs 263 ng mg(-1) protein, P < 0.001). For this group of patients Cath H tumour levels correlated with the survival rat...
Cathepsin A activity in primary and metastatic human melanocytic tumors
Archives of Dermatological Research, 2000
Several lysosomal proteases including cathepsins B, D, H and L have been found to play a role in the metastasis of tumor cells. However, up to now no information on the role of cathepsin A, a lysosomal multifunctional peptidase, in the proliferative, invasive, and metastatic potential of malignant tumors has been available. In the present study we compared the activity of cathepsin A in lysates of 34 human melanocytic tumors: primary (n = 12) and metastatic (n = 5) malignant melanoma, dysplastic pigmented nevi (n = 6) and pigmented nevi without evidence of dysplastic melanocytes (n = 11). The carboxypeptidase activity of cathepsin A was assayed at pH 5.0 with its specific substrate Cbz-Phe-Ala. The amount of released C-terminal alanine was measured by the ninhydrin method. We found that lysates of primary malignant melanoma lesions exhibited significantly higher cathepsin A activity than lysates of dysplastic and normal pigmented nevi. The cathepsin A activity in lysates of metastatic lesions of malignant melanoma was significantly higher than in primary focus lysates. It seems that cathepsin A may play a role in malignant transformation and metastatic dissemination of malignant melanoma.