Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
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Advances in Clinical and Experimental Medicine

2009, vol. 18, nr 1, January-February, p. 41–45

Publication type: original article

Language: English

Comparison of Cathepsin B Activity and the Ratio of Cathepsin B to Cysteine Peptidase Inhibitor in Human Colorectal Cancer Tissue

Porównanie aktywności katepsyny B i indeksu katepsyna B/inhibitory peptydaz cysteinowych w ludzkiej tkance nowotworów okrężniczo−odbytniczych

Tadeusz Sebzda1,, Jakub Gburek2,, Marek Rząca3,, Monika Pfanhauser3,, Witold Pilecki1,, Maciej Siewiński4,, Maria Warwas2,

1 Department of Pathophysiology, Wrocław Medical Unversity, Poland

2 Department of Pharmaceutical Biochemistry, Wrocław Medical Unversity, Poland

3 Regional Specialist Hospital, Wrocław, Poland

4 Faculty of Public Health, Wrocław Medical Unversity, Poland

Abstract

Background. Cathepsin B (CB), which is inhibited by cysteine peptidase inhibitors (CPIs), plays an important role in the process of cancer invasion and metastasis.
Objectives. The aim of this study was to compare CB and low−molecular−weight CPI activities in the extracts of human colorectal carcinoma tissues from the center of the tumor and the tumor−free area 2 cm and 5 cm from the tumor border in order to examine their significance in this type of cancer.
Material and Methods. CB activity was measured using a flurogenic substrate and CPI using a colorimetric substrate as anipapain activity. The CB:CPI ratio was also calculated.
Results. The activities were significantly higher in the tumor tissue extracts than in the controls (p ≤ 0.0001). CB was elevated 26−fold and CPI 2−fold. Only cathepsin B activity decreased significantly with distance from the tumor border (p ≤ 0.0001). CB and CPI activities as well as the CB:CPI ratio increased with the stage of tumor tissue differentiation grade. Conclusion. The results provided convincing evidence that the distribution of CB and CPI may be important for colorectal cancer invasion. CB activity of cancerous tissue extracts can be an additional marker of tissue differentiation grade. For patients with marked elevation of CB activity in the cancer tissue, relatively extensive resection may be necessary.

Streszczenie

Wprowadzenie. Katepsyna B (CB), hamowana przez inhibitory peptydaz cysteinowych (CPI), odgrywa istotną rolę zarówno w powstawaniu, jak i inwazji procesu nowotwowego.
Cel pracy. Porównanie i poznanie istotności ekspresji CB oraz CPI w ekstraktach ludzkich nowotworów okrężniczo−odbytniczych z tkanek pobranych ze środka guza (0) oraz w odległości 2 i 5 cm.
Materiał i metody. Aktywność CB oznaczano metodą fluorometryczną, a aktywność CPI metodą kolorymetryczną jako aktywność antypapainową. Obliczano również indeks CB/CPI.
Wyniki. Oznaczane aktywności były istotnie wyższe w ekstraktach tkanek nowotworowych w stosunku do grupy kontrolnej (p < 0,001). CB rosła 26−krotnie, a CPI 2−krotnie. Jedynie aktywność CB malała istotnie statystycznie (p < 0.001) wraz z odległością od środka guza. Wszystkie oznaczane wskaźniki rosły wraz ze stopniem zróżnicowania guza, ale różnice nie miały charakteru istotnie statystycznego.
Wnioski. Rezultaty pracy wskazują, że dystrybucja ekspresji CB i CPI jest istotna dla inwazji nowotworów okrężniczo−odbytniczych. Oznaczanie aktywności CB może być pomocne w określeniu stopnia zróżnicowania tkanek guza. U chorych ze znacznym wzrostem aktywności CB w ekstraktach tkankowych byłaby wskazana jak największa resekcja guza.

Key words

colorectal cancer, cathepsin B activity, cysteine peptidase inhibitors, cystatins

Słowa kluczowe

rak okrężniczo−odbytniczy, aktywność katepsyny B, inhibitory peptydaz cysteinowych, cystatyny

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