interleukin-8 and Adenocarcinoma--Clear-Cell

Ovarian Cancer is the leading cause of death from gynecological malignancy. The poor prognosis is mainly due to presentation at a late stage and poor response to therapy. Much research is needed to identify diagnostic and prognostic biomarkers as well as therapeutic targets for ovarian cancer. Interleukin-8 is expressed by many tumour types and is known to have mitogenic, motogenic and angiogenic effects on tumour cells.. The aim of this study was to investigate the expression of IL-8 and IL-8 receptors (IL-8RA and IL-8RB) in different histological subtypes of ovarian tumours, as potential prognostic biomarkers in ovarian tumours.. Immunohitochemistry was used to study the expression of IL-8 and IL-8 receptors in 115 ovarian tumours including 21 benign tumours, 25 borderline tumours and 69 carcinomas of serous, clear cell, endometrioid and mucinous types. The correlation of expression profile, tumour type, stage, and progression free survival and overall survival was statistically analysed.. IL-8 and IL-8 receptors were expressed in all types of tumours with variable intensity and subcellular distribution. There was a statistically significant correlation between levels of expression and tumour stage and tumour type, being mostly significant in serous tumours. No correlation with patient progression free survival or overall survival was found.. This is the first study investigating the expression of IL-8 and IL-8 receptors using immunohistochemistry in different types of ovarian tumours, including benign and borderline tumours. IL-8 and IL-8RA are potential prognostic biomarkers and therapeutic targets in ovarian cancer, particularly in ovarian serous carcinoma.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Carcinoma, Endometrioid; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous; Disease-Free Survival; Female; Humans; Interleukin-8; Neoplasm Staging; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Prognosis; Receptors, Interleukin-8; Survival

Monocytes/macrophages (MO/MA) are an important but heterogeneous population of immune inflammatory cells that have diverse effector functions. We examined and compared these differences in peripheral blood and ascites of epithelial ovarian cancer patients with peripheral blood of normal donors.. Comparisons were made of cell surface subsets, cytokine production, and FcR-dependent cytotoxicity of CD14+ MO/MA and the CD14brightCD16-HLA-DR+ MO/MA subset in normal donor peripheral blood and peripheral blood and ascites from epithelial ovarian cancer patients. Studies were done on monocyte-derived macrophages cultured with macrophage colony-stimulating factor and activated with lipopolysaccharide or a combination of lipopolysaccharide plus recombinant IFN-gamma.. We determined that MO/MA or its subset from epithelial ovarian cancer patients had altered morphology and significantly less antibody-dependent cell-mediated cytotoxicity and phagocytic activity than did MO/MA from normal donors. Our findings also showed that monocyte-derived macrophages from both epithelial ovarian cancer patients and normal donors produce macrophage colony-stimulating factor-stimulated cytokines, including interleukin-8, tumor necrosis factor-alpha, and interleukin-6.. These findings highlight for the first time the defective antibody-dependent cell-mediated cytotoxicity and phagocyte functions of epithelial ovarian cancer-associated MO/MA, which could have implications for immunobiotherapeutic strategies.

Topics: Adenocarcinoma, Clear Cell; Antibody-Dependent Cell Cytotoxicity; Ascitic Fluid; Carcinoma, Endometrioid; Carcinoma, Papillary; Female; HLA-DR Antigens; Humans; Interleukin-6; Interleukin-8; Lipopolysaccharide Receptors; Macrophages; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms; Peritoneal Neoplasms; Phagocytosis; Receptors, IgG; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

We examined the antiproliferative effect of IFN-alphaCon1 and its mechanism on ovarian clear cell adenocarcinoma in vitro and in vivo.. (a) The effects of IFN-alphaCon1 on growth, morphology, cell cycle, and type I IFN-alpha receptor (IFNAR-2) expression were examined on two ovarian clear cell adenocarcinoma cell lines (KOC-5C and KOC-7C) in vitro. (b) KOC-5C or KOC-7C cells were transplanted into nude mice, and changes in tumor volume, tumor weight, apoptosis, necrosis, and microvessel density were investigated. The expression of angiogenesis factors was examined in the serum and the developed tumors.. Both cell lines expressed IFNAR-2 mRNA, but its protein was detected only in KOC-7C. In KOC-7C cells, antiproliferative effects were observed in a time- and dose-dependent manner and cell division was blocked at the S phase. The KOC-7C tumors showed decreases in tumor volume and weight; a decreasing tendency in basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and interleukin (IL)-8 protein expression in the tumor; a significant decrease in bFGF and IL-8 protein expression in the serum, and of microvessel density; and significant increase in apoptosis and necrosis in the tumor. In the KOC-5C tumors, these in vitro and in vivo changes were not apparent, and the antiproliferative effects of IFN-alphaCon1 were not obvious.. IFN-alphaCon1 suppresses tumor proliferation by inducing apoptosis, blocking the cell cycle, and inhibiting tumor angiogenesis. Our findings show that the clinical efficacy of IFN-alphaCon1 can be predicted by examining IFNAR-2 expression on tumor cells, and the efficacy of IFN-alphaCon1 treatment can be evaluated by measuring serum bFGF and IL-8 levels.

Topics: Adenocarcinoma, Clear Cell; Animals; Antiviral Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Female; Fibroblast Growth Factor 2; Flow Cytometry; Humans; Interferon Type I; Interferon-alpha; Interleukin-8; Membrane Proteins; Mice; Mice, Inbred BALB C; Mice, Nude; Microcirculation; Necrosis; Ovarian Neoplasms; Receptor, Interferon alpha-beta; Receptors, Interferon; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Time Factors; Vascular Endothelial Growth Factor A