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Biological Chemistry

Editor-in-Chief: Brüne, Bernhard

Editorial Board Member: Buchner, Johannes / Ludwig, Stephan / Sies, Helmut / Turk, Boris / Wittinghofer, Alfred

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Disease processes may be reflected by correlations among tissue kallikrein proteases but not with proteolytic factors uPA and PAI-1 in primary ovarian carcinoma

Julia Dorn1 / Nadia Harbeck2 / Ronald Kates3 / Viktor Magdolen4 / Linda Grass5 / Antoninus Soosaipillai6 / Barbara Schmalfeldt7 / Eleftherios P. Diamandis8 / Manfred Schmitt9

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Corresponding author

Citation Information: Biological Chemistry. Volume 387, Issue 8, Pages 1121–1128, ISSN (Online) 1437-4315, ISSN (Print) 1431-6730, DOI: 10.1515/BC.2006.138, August 2006

Publication History

Received:
November 30, 2005
Accepted:
May 11, 2006
Published Online:
2006-08-09

Abstract

In epithelial ovarian cancer, the high mortality rate is usually ascribed to late diagnosis, since these tumors commonly lack early-warning symptoms, but tumor-associated biomarkers useful for prognosis or therapy response prediction are in short supply. However, members of the tissue kallikrein serine protease family, the serine protease uPA and its inhibitor PAI-1, are associated with tumor progression of ovarian cancer. Therefore, we used ELISA to determine uPA, PAI-1, and tissue kallikreins hK5–8, 10, 11, and 13 in extracts of 142 primary tumor tissue specimens from ovarian cancer patients and studied the strength of association between protein expression levels of these tumor tissue-associated factors. uPA, PAI-1, hk5, and hk8 were related to FIGO stage; hK5 expression was higher in FIGO III/IV than in FIGO I/II patient tissues. PAI-1 and hk5 differed significantly according to nuclear grading; expression of hK5 was higher in G3 than in G1/2 tumors. Associations between uPA, PAI-1, and the tissue kallikreins were weak. There were strong pairwise correlations within the cluster of tissue kallikreins hK5, 6, 7, 8, 10, and 11, but their bivariate distributions depended on nuclear grading. These results support the notion that several tissue kallikreins are co-expressed in ovarian cancer patients, substantiating the existence of a steroid hormone-driven tissue kallikrein cascade in this disease.

Keywords: ovarian cancer; PAI-1; plasminogen activator; plasminogen activator inhibitor type-1; proteolytic factors; tissue kallikreins; uPA; urokinase

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