Abstract
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–1protein, P< 0.001). For this group of patients Cath H tumour levels correlated with the survival rate, while for the entire patient population this was not the case. Smokers with high tumour levels of Cath H experienced poor survival. Cath H was significantly higher in sera of patients with malignant and benign lung diseases than in control sera (P< 0.001). The increase was significant for all histological types, being the highest in small-cell and squamous cell carcinomas. Our study reveals that in lung tumours there is different behaviour of Cath H compared with other cysteine peptidases, e.g. cathepsin B and cathepsin L. Variations between tissue and serum levels of Cath H indicate either reduced expression or enhanced secretion of this enzyme in lung tumours. © 2000 Cancer Research Campaign
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References
Abel U, Berger J and Wiebelt H (1984) An exploratory procedure for the evaluation of quantitative prognostic factors. Methods Inf Med 23: 154–156
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye-binding. Anal Biochem 72: 248–254
Budihna M, Strojan P, S̆mid L, S̆krk J, Vrhovec J, Z̆upevc A, Rudolf Z, Z̆argi M, Kras̆ovec M, Svetic B, Kopitar-Jerala N and Kos J (1996) Prognostic value of cathepsins B, H, L, D and their endogenous inhibitors stefins A and B in head and neck carcinoma. Biol Chem Hoppe-Seyler 377: 385–390
Chang JC, Lesser M, Yoo OH and Orlowski M (1986) Increased cathepsin B-like activity in alveolar macrophages and bronchoalveolar lavage fluid from smokers. Am Rev Respir Dis 134: 538–541
Chapman HA, Riese RJ and Shi G-P (1997) Emerging roles for cysteine proteases in human biology. Annu Rev Physiol 59: 63–88
Duffy MJ (1996) Proteases as prognostic markers in cancer. Clin Cancer Res 2: 613–618
Ebert W, Knoch H, Werle B, Trefz G, Muley TH and Spiess E (1994) Prognostic value of increased lung tumor tissue cathepsin B. Anticancer Res 14: 895–900
Ebert E, Werle B, Julke B, Kopitar-Jerala N, Kos J, Lah T, Abrahamson M, Spiess E and Ebert W (1997) Expression of cysteine protease inhibitors stefin A, stefin B, and cystatin C in human lung tumor tissue. Adv Exp Med Biol 421: 259–265
Gabrijelc̆ic̆ D, Svetic B, Spaic̆ D, S̆krk J, Budihna M, Dolenc I, Popovic̆ T, Cotic̆ V and Turk V (1992) Cathepsins B, H and L in human breast carcinoma. Eur J Clin Chem Clin Biochem 30: 69–74
Gairola CG, Galicki NI, Cardozo C, Lai YL and Lesser M (1989) Cigarette smoke stimulates cathepsin B activity in alveolar macrophages of rats. J Lab Clin Med 114: 419–425
Hermenek P and Sobin L (1987). UICC TNM classification of malignant tumors, Springer Verlag: Berlin
Inoue T, Ishida T, Sugio K and Sugimachi K (1994) Cathepsin B expression and laminin degradation as factors influencing prognosis of surgically treated patients with lung adenocarcinoma. Cancer Res 54: 6133–6136
Ishii Y, Hashizume Y, Kominami E and Uchiyama Y (1991a) Changes in immunoreactivity for cathepsin H in rat type II alveolar epithelial cells and its proteolytic activity in bronchoalveolar lavage fluid over 24 hours. Anat Rec 230: 519–523
Ishii Y, Hashizume Y, Watanabe T, Waguri S, Sato N, Yamamoto M, Hasegawa S, Kominami E and Uchiyama Y (1991b) Cysteine proteinases in bronchoalveolar epithelial cells and lavage fluid of rat lung. J Histochem Cytochem 39: 461–468
Kaplan EL and Meier P (1958) Non-parametric estimation from incomplete observation. J Am Stat Assoc 53: 457–481
Kirschke H, Barrett AJ and Rawlings BJ (1995) Proteinases 1: lysosomal cysteine proteinases. Protein Profile, Sheterline P (ed), pp. 1584–1620, Academic Press: London
Knoch H, Werle B, Ebert W and Spiess E (1994) Imbalance between cathepsin B and cysteine proteinase inhibitors is of prognostic significance in human lung cancer. Int J Oncol 5: 77–85
Koga H, Mori N, Yamada H, Nishimura Y, Tokuda K, Kato K and Imoto T (1992) Endo-and aminopeptidase activities of rat cathepsin H. Chem Pharm Bull 40: 965–970
Kos J and Lah TT (1998) Cysteine proteinases and their endogenous inhibitors: target proteins for prognosis, diagnosis and therapy in cancer (review). Oncol Rep 5: 1349–1361
Kos J, S̆mid A, Kras̆ovec M, Svetic B, Lenarc̆ic̆ B, Vrhovec I, S̆krk J and Turk V (1995) Lysosomal proteinases cathepsins D, B, H, L and their inhibitors stefins A and B in head and neck cancer. Biol Chem Hoppe-Seyler 376: 401–405
Kos J, S̆tabuc B, Schweiger A, Kras̆ovec M, Cimerman N, Kopitar-Jerala N and Vrhovec I (1997) Cathepsins B, H, and L and their inhibitors stefin A and cystatin C in sera of melanoma patients. Clin Cancer Res 3: 1815–1822
Krepela E, Kasafirek E, Novak K and Viklicky J (1990) Increased cathepsin B activity in human lung tumors. Neoplasma 37: 61–70
Ledakis P, Tester WT, Rosenberg N, Romero-Fischmann D, Daskal I and Lah TT (1996) Cathepsins D, B, and L in malignant human lung tissue. Clin Cancer Res 2: 561–568
Lesser M, Galicki N, Cardozo C and Gairola CG (1989) Cathepsin L activity in alveolar macrophages of rats: response to cigarette smoke. Am J Respir Cell Mol Biol 1: 371–376
Manegold C and Drings P (1998) Chemotherapie des nichtkleinzelligen Lungenkarzinoms. In: Thoraxtumoren: Diagnostik – Staging – gegenwärtiges Therapiekonzept, Drings P, Vogt-Moykpf I (eds), pp. 310–327, Springer Verlag: Heidelberg
McCaughan BC, Martini N and Bains MS (1985) Bronchial carcinoids: review of 124 cases. J Thorac Cardiovasc Surg 89: 8–17
Mountain CF (1991) Surgical treatment of lung cancer. Critic Rev Oncol/Hematol 11: 179–207
Ohwada A, Takahshi H, Nagaoka I, Iwabuchi K, Mikami K and Kira S (1995) Effect of cigarette smoke on the mRNA and protein expression of carcinoembryonic antigen (CEA), a possible chemoattractant for neutrophils in human bronchioloalveolar tissues. Thorax 50: 651–657
Qian F, Chan SJ, Gong Q, Bajkowski AS, Steiner DF and Frankfater A (1991) The expression of cathepsin B and other lysosomal proteinases in normal tissues and in tumors. Biomed Biochim Acta 50: 531–540
San Segundo B, Chan SJ and Steiner DF (1986) Differences in cathepsin B mRNA levels in rat tissues suggest specialized functions. FEBS Lett 201: 251–256
Schiller JH (1998) Lung cancer: therapeutic modalities and cytoprotection. Lung 176: 145–164
Schmitt M, Jänicke F and Graeff H (1992) Tumor-associated proteases. Fibrinolysis 6: 3–26
Schraube P, Kimmig B, Latz D, Flentje M and Wannenmacher M (1998) Radiotherapie des Bronchialkarzinoms. In Thoraxtumoren: Diagnostik – Staging – gegenwärtiges Therapiekonzept, Drings P, Vogt-Moykopf I (eds), pp. 277–295, Springer Verlag: Heidelberg
Schweiger A, S̆tabuc B, Popovic̆ T, Turk V and Kos J (1997) Enzyme-linked immunosorbent assay for the detection of total cathepsin H in human tissue cytosols and sera. J Immunol Methods 201: 165–172
Sivaparvathi M, Sawaya R, Gokaslan ZL, Chintala KS and Rao JS (1996) Expression and the role of cathepsin H in human glioma progression and invasion. Cancer Lett 104: 121–126
Sloane BF, Moin K and Lah TT (1994) Regulation of lysosomal endopeptidases in malignant neoplasia. In: Biochemical and Molecular Aspects of Selected Cancers, Pretlow TG, Pretlow TP (eds), pp. 411–472, Academic Press: New York
Sukoh N, Shosaku A, Ogura S, Isobe H, Takekawa H, Inoue K and Kawakami Y (1994) Immunohistochemical study of cathepsin B. Prognostic significance in human lung cancer. Cancer 74: 46–51
Takahashi H, Ishidoh K, Muno D, Ohwada A, Nukiwa T, Kominami E and Kira S (1993) Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. Am Rev Respir Dis 147: 1562–1568
Treftz G, Lüthgens K, Erdel M, Spiess E and Ebert W (1989) Plasminogen activator and cathepsin B in normal and malignant human lung tissue. J Cancer Res Clin Oncol 115: S50
Uchiyama Y, Waguri S, Sato N, Watanabe T, Ishido K and Kominami E (1994) Review: cell and tissue distribution of lysosomal cysteine proteinases, cathepsins B, H and L, and their biological roles. Acta Histochem Cytochem 27: 287–308
Werle B, Ebert W, Klein W and Spiess E (1995) Assessment of cathepsin L activity by use of the inhibitor CA-074 compared to cathepsin B activity in human lung tumor tissue. Biol Chem Hoppe-Seyler 376: 157–164
Werle B, Jülke B, Lah T, Kos J, Spiess E and Ebert W (1997a) Cathepsin B and Cathepsin L: prognostic factors in human lung cancer?. In: Proteolysis in Cell Function, Hopsu-Havu VK, Jarvinen M, Kirschke H (eds), pp. 472–478, IOS Press: Amsterdam
Werle B, Jülke B, Lah T, Spiess E and Ebert W (1997b) Cathepsin B fraction active at physiological pH of 7.5 is of prognostic significance in squamous cell carcinoma of human lung. Br J Cancer 75: 1137–1143
Werle B, Lötterle H, Schanzenbächer U, Lah TT, Kalman E, Kayser K, Bülzebruck H, Schirren S, Krasovec M, Kos J and Spiess E (1999a) Immunochemical analysis of cathepsin B in lung tumours: an independent prognostic factor for squamous cell carcinoma patients. Br J Cancer 81: 510–519
Werle B, Staib A, Jülke B, Ebert W, Zladoidsky P, Sekirnik A, Kos J and Spiess E (1999b) Fluorometric microassays for the determination of cathepsin L and cathepsin S activities in tissue extracts. Biol Chem 380: 1109–1116
WHO (1981). Histological Classification of Lung Tumours, World Health Organization: Geneva
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Schweiger, A., Staib, A., Werle, B. et al. Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking. Br J Cancer 82, 782–788 (2000). https://doi.org/10.1054/bjoc.1999.0999
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DOI: https://doi.org/10.1054/bjoc.1999.0999
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