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J.
Cancer Mol. 2: 67-72, 2006
[Research Paper]
Cathepsin B and Cysteine Protease Inhibitors in Human Tongue Cancer:
Correlation with Tumor Staging and In Vitro Inhibition of
Cathepsin B by Chicken Cystatin
Yousif Saleh, Jan Wnukiewicz, Ryszard
Andrzejak, Tadeusz Trziszka, Maciej Siewinski,
Piotr Ziolkowski, and Wieslaw Kopec
Department of Forensic Medicine, Molecular Technical Unit [Y. Saleh],
Department of Oral and Maxillo-Facial Surgery [J.
Wnukiewicz], Department of Internal Medicine, Occupational Diseases
and Hypertension [R. Andrzejak],
Faculty of Public Health [M.
Siewinski], and Department of
Pathology [P. Ziolkowski], Wroclaw Medical University, Wroclaw,
Poland; Department of Animal Products, Wroclaw Agriculture
University, Wroclaw, Poland [T. Trziszka,
W. Kopec]
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 patientsˇ¦
cathepsin
B activities in sera.
(Keywords:
cathepsin B; chicken cystatin; tongue cancer; cysteine protease)
Received
1/3/06; Revised 1/30/06; Accepted 2/8/06.
1Correspondence:
Dr. Yousif Saleh,
Department of Forensic Medicine, Molecular Technical Unit, Wroclaw
Medical University, Sklodowskiej-Curie-52, 50-369 Wroclaw, Poland.
Phone: 48-717841588. E-mail: biolcancer@op.pl |
