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Originally published In Press as doi:10.1074/jbc.M112275200 on April 26, 2002

J. Biol. Chem., Vol. 277, Issue 27, 24584-24593, July 5, 2002
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Identification of Biologically Active Chemokine Isoforms from Ascitic Fluid and Elevated Levels of CCL18/Pulmonary and Activation-regulated Chemokine in Ovarian Carcinoma*

Evemie SchutyserDagger , Sofie StruyfDagger §, Paul ProostDagger §, Ghislain OpdenakkerDagger , Geneviève Laureys, Bruno Verhasselt, Lieven Peperstraete||, Ignace Van de Putte||, Alessandra Saccani**, Paola Allavena**, Alberto Mantovani**, and Jo Van DammeDagger Dagger Dagger

From the Dagger  Laboratory of Molecular Immunology, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium, the  University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium, || Regional Hospital Heilig Hart, Naamsestraat 105, B-3000 Leuven, Belgium, and ** Laboratory of Immunology, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, I-20157 Milano, Italy

Chemokines are important in leukocyte homeostasis, inflammation, angiogenesis, and metastasis. Here, the molecular diversity of chemokines present in ovarian carcinoma was studied by purifying the proteins to homogeneity from ascitic fluid. Biologically active intact CCL2 and processed CXCL8, CCL3, and CCL18 isoforms were recovered. CCL7 and CCL20 were also purified, but their levels were 10-fold lower compared with CXCL8, CCL2, and CCL3 and even 100-fold lower than the amounts of CCL18 isolated. In ascitic fluids from patients with ovarian carcinoma (n = 12), significantly higher levels of CXCL8 and CCL18 (2.0 versus 0.7 ng/ml (p = 0.01) and 120 versus 44 ng/ml (p = 0.0002), respectively) were detected compared with those in nonovarian carcinoma patients (n = 12). In contrast to CXCL8, CCL18 was not inducible in carcinoma cell lines. Immunostaining showed CCL18 expression in tumor-infiltrating cells with monocyte/macrophage morphology but not in the ovarian carcinoma cells. Our data demonstrate that biochemically heterogenous but biologically active forms of several chemokines are present at different concentrations in ovarian carcinoma ascitic fluid. This points to a delicate balance of chemokines in epithelial ovarian cancer and to a potentially major role for CXCL8 and CCL18 in this tumor.

* This work was supported by the Fund for Scientific Research of Flanders (FWO-Vlaanderen), the Concerted Research Actions of the Regional Government of Flanders, the InterUniversity Attraction Pole Initiative of the Belgian Federal Government, the Belgian Federation against Cancer, the Fortis AB Cancer Research Fund, and the Biomed and Biotech Programs of the European Community.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a fellowship from the FWO-Vlaanderen.

Dagger Dagger To whom correspondence should be addressed. Tel.: 32-16-337348; Fax: 32-16-337340; E-mail: jozef.vandamme@rega.kuleuven.ac.be.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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