The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer.
OBJECTIVE
The aim of this study was to investigate the contribution of cathepsin B and cystatin C to the mechanisms of invasion by ovarian cancer.


METHODS
Using surgical materials from patients with ovarian cancer, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting analysis were performed using antibodies against cathepsin B or cystatin C. Serum levels of cathepsin B and cystatin C in patients with benign and malignant ovarian lesions were determined by enzyme-linked immunosorbent assay (ELISA). An invasion assay using an ovarian cancer cell line was performed by addition of cystatin C or specific inhibitors of cathepsin B.


RESULTS
While immunohistochemical staining of cathepsin B and cystatin C was evident in cancer cells and associated stromal tissue, this was not the case in benign tumors. The malignancies were also found to be positive for cathepsin B and cystatin C by SDS-PAGE and Western blotting analysis. No significant difference in serum cathepsin B levels was observed between patients with benign and malignant disease. However, the concentration of cystatin C in cases with ovarian cancer was significantly higher in benign cases (P<0.0001) and in healthy controls (P<0.0001). Invasion by cancer cells was dose-dependently suppressed by cystatin C and cathepsin B inhibitors.


CONCLUSIONS
The results provided convincing evidence that cathepsin B and cystatin C may contribute to the mechanisms of invasion of ovarian cancer.
Department of Obstetrics and Gynecology, Nagoya City University Medical School, Mizuho-cho, Mizuho, Nagoya 467-8601, Japan. og.nishi@med.nagoya-cu.ac.jp
Hiroshi
H
Nishikawa
Yasuhiko
Y
Ozaki
Tamao
T
Nakanishi
Klas
K
Blomgren
Toyohiro
T
Tada
Atsushi
A
Arakawa
Kaoru
K
Suzumori
D000293:Adolescent; D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002401:Cathepsin B / Q000097:blood / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D055316:Cystatin C; D015891:Cystatins / Q000097:blood / Q000502:physiology*; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology*
C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D002401:Cathepsin B