Advanced
ovarian cancer is a devastating disease. Gaining
biomarkers of early detection during ovarian
tumorigenesis may lead to earlier diagnosis and better therapeutic strategies.
Cystatin B (CSTB) functions as an inhibitor to suppress intracellular
cysteine proteases and has been implicated in several types of
cancers. The present study explored the expression of CSTB in human ovarian
tumors, to investigate CSTB expression associated with clinicopathological features, and to examine the effect of
transforming growth factor-β (TGF-β), which plays a key role in ovarian
tumorigenesis, on CSTB expression in
ovarian cancer cells. The ovarian tissue samples from 33 patients were retrieved. The expression of CSTB in ovarian tissue was examined by immunohistochemistry. We found that CSTB was over-expressed in human ovarian surface epithelial
tumors, including serous, mucinous and clear cell
tumors. The immunoreactive staining of CSTB was strong in borderline and malignant
tumors, weak in benign
tumors, and negative in normal tissue counterparts, but was not correlated with the clinicopathological features of patients with ovarian
tumors, such as age, histological types,
tumor size,
lymph node metastasis and clinical stages. The CSTB at
mRNA and
protein levels in two types of
epithelial ovarian cancer cells, OVCAR-3 and SK-OV-3, was decreased after TGF-β1 treatment detected by quantitative PCR and western blot analysis, respectively. The inhibitory effect of TGF-β1 on CSTB expression was abolished in the presence of
SB-431542, a TGF-β type I receptor
kinase inhibitor. Our data suggest that CSTB is
tumor tissue-specific and overexpressed in ovarian borderline and malignant
tumors. The increased CSTB expression in ovarian tissue represents
tumor progression and is dysregulated by the TGF-β signaling pathway. CSTB may become a novel diagnostic intracellular
biomarker for the early detection of
ovarian cancer.