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Cathepsin B and Cysteine Protease Inhibitors in Human Tongue Cancer: Correlation with Tumor Staging and In Vitro Inhibition of Cathepsin B by Chicken Cystatin

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Author(s): Yousif Saleh | Jan Wnukiewicz | Ryszard Andrzejak | Tadeusz Trziszka | Maciej Siewinski | Piotr Ziolkowski | Wieslaw Kopec

Journal: Journal of Cancer Molecules
ISSN 1816-0735

Volume: 2;
Issue: 2;
Start page: 67;
Date: 2006;
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Keywords: cathepsin B | chicken cystatin | tongue cancer | cysteine protease

ABSTRACT
AIM: The study is aimed to investigate if the sera and the tumor tissues of tongue cancer patients demonstrate elevated cathepsin B activity during cancer progression and in vitro inhibition of the activity of cathepsin B by chicken cystatin.METHODS: Pro-cathepsin B and cathepsin B activities and cystatins as antipapain activity were measured using a fluorogenic substrate in 47 sera from patients and compared with 40 control subjects. Peroxidase method was used for immunohistochemical staining.RESULTS: The activities of pro-cathepsin B and cathepsin B were found to be significantly increased and their endogenous inhibitor cystatin C decreased in the sera of patients with tongue cancer. Patients with advanced stages had higher serum activities of pro-cathepsin B, cathepsin B and cysteine protease inhibitors if compared with the patients with stage I disease. However, the levels of cysteine protease inhibitors were not comparable to those of cathepsin B. The serum activity of cathepsin B from tongue cancer patients could be decreased by 2.4-fold after treatment with 5 nM purified egg white cystatin. Immunohistochemical staining showed significantly increased expression of cystatin C and cathepsin B in tongue tumor tissues, while negative staining was observed with the non-tumor parts.CONCLUSION: Elevated cathepsin B level was closely correlated with the invasion and progression of tongue cancer. The incomparable levels between cathepsin B and its natural inhibitors could contribute to the uncontrolled proteolysis and thus the malignant progression of tongue cancer. Chicken cystatin was able to effectively inhibit patients’ cathepsin B activities in sera.
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