Expression of high molecular weight cysteine proteinase inhibitor in ovarian cancer tissues and regulation of cathepsin B expression by placental CPI.

Yousif Saleh1, PhD, Maciej Siewinski2, PhD, Andrzej Popiela2, MD,PhD, Piotr Ziólkowski1, MD, PhD, Michal Jelen1, MD, PhD, Jacek Rybka3, PhD,

1Department of Pathology, Medical University of Wroclaw, 10 Chalubinskiego St., 50-368 Wroclaw, Poland. 2 Department of Obstetrics and Gyneacology Medical University of Wroclaw, 3 Chalubinskiego 3 Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 12 Weigla St, 53 -114 Wroclaw, Poland.

Cysteine proteinase inhibitor (CPI) synthesis of human placenta was demonstrated by immunohistochemical staining and Western blotting. In Western blotting mouse polyclonal antibodies to placental CPI reacted with the placental CPI molecular weight 67 kDa, and by double immunodiffusion CPI present in ovarian cancer homogenate and serum were shown to react with the same antiserum to CPI. Immunohistochemical staining was shown Significantly, positive expression of high molecular weight CPI was observed on the tumor cell surface in serous, and endometrioid ovarian carcinomas with metastasis. It was found that normal endometrioid was not stained with anti-placental CPI antibody. Cathepsin B and its pro-cathepsin B median level enzymatic activities in ovarian cancer tissue homogenates increased progressively with FIGO stage of the disease. The enzyme level decreased 22-fold after treatment of tissue homogenates with 5 nM of purified CPI. These results provide evidence that addition of CPI reduces the levels of cysteine type cathepsins to that of normal noncancerous values.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Molecular Pathology.