The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer
The role of cathepsin B and cystatin C in the mechanisms of invasion by ovarian cancer
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DOI：
10.1016/j.ygyno.2003.11.017
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发表时间：
2004-03-01
影响因子：
4.7
通讯作者：
Suzumori, K
中科院分区：
文献类型：
--
作者：
Nishikawa, H;Ozaki, Y;Suzumori, K
目标。本研究旨在探讨组织蛋白酶B和胱抑素C在卵巢癌侵袭机制中的作用。材料和方法。采用免疫组化、十二烷基硫酸钠-聚丙烯酰胺凝胶电泳（SDS-PAGE）和Western blotting检测卵巢良恶性病变患者血清组织蛋白酶B和胱抑素C水平，采用酶联免疫吸附试验（ELISA）。通过添加胱抑素C或特定的组织蛋白酶b抑制剂，对卵巢癌细胞系进行了侵袭试验。虽然组织蛋白酶B和胱抑素C的免疫组化染色在癌细胞和相关的间质组织中很明显，但在良性肿瘤中却没有这种情况。通过SDS-PAGE和Western blotting分析，发现恶性肿瘤组织蛋白酶B和胱抑素C阳性。良恶性疾病患者血清组织蛋白酶B水平无明显差异。而良性卵巢癌患者血清胱抑素C浓度显著高于健康对照组（P < 0.0001） （P < 0.0001）。胱抑素C和组织蛋白酶B抑制剂可呈剂量依赖性地抑制癌细胞的侵袭。这些结果为组织蛋白酶B和胱抑素C可能参与卵巢癌的侵袭机制提供了令人信服的证据。(C) 2004爱思唯尔公司版权所有。
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.Materials and 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 immumosorbent 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.Conclusion. The results provided convincing evidence that cathepsin B and cystatin C may contribute to the mechanisms of invasion of ovarian cancer. (C) 2004 Elsevier Inc. All rights reserved.