title: Identification of biologically active chemokine isoforms from ascitic fluid and elevated levels of CCL18/pulmonary and activation-regulated chemokine in ovarian carcinoma.
abstract: 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.
authors.affiliation: Laboratory of Molecular Immunology, Rega Institute for Medical Research, K.U. Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
authors.forename: Evemie
authors.initials: E
authors.lastname: Schutyser
authors.forename: Sofie
authors.initials: S
authors.lastname: Struyf
authors.forename: Paul
authors.initials: P
authors.lastname: Proost
authors.forename: Ghislain
authors.initials: G
authors.lastname: Opdenakker
authors.forename: Genevieve
authors.initials: G
authors.lastname: Laureys
authors.forename: Bruno
authors.initials: B
authors.lastname: Verhasselt
authors.forename: Lieven
authors.initials: L
authors.lastname: Peperstraete
authors.forename: Ignace
authors.initials: I
authors.lastname: Van de Putte
authors.forename: Alessandra
authors.initials: A
authors.lastname: Saccani
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.forename: Alberto
authors.initials: A
authors.lastname: Mantovani
authors.forename: Jo
authors.initials: J
authors.lastname: Van Damme
mesh_terms: D001201:Ascites / Q000473:pathology / Q000503:physiopathology*; D018925:Chemokines / Q000502:physiology*; D019742:Chemokines, CC / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D010051:Ovarian Neoplasms / Q000473:pathology / Q000503:physiopathology*; D020033:Protein Isoforms / Q000502:physiology; D014407:Tumor Cells, Cultured
chemical_list: C111792:CCL18 protein, human; D018925:Chemokines; D019742:Chemokines, CC; D020033:Protein Isoforms