Abstract
BackgroundWe previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. Here, we examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes.MethodsExpression patterns of selected inflammatory genes were mined from our previously published data base. Bilateral pelvic peritoneal and subjacent stromal specimens were obtained from 20 women with EOC and 7 women with benign pelvic conditions. Sections were first stained by indirect immunoperoxidase and numbers of monocytes/macrophages (MO/MA), T cells, B cells, and NK cells counted. Proportions of CD68+ cells and CD3+ cells that coexpressed MO/MA differentiation factors (CD163, CCR1, CXCR8, VCAM1, and phosphorylated cytosolic phospholipase A2 [pcPLA2]), which had demonstrated expression in EOC peritoneal samples, were determined by multicolor immunofluorescence.ResultsMO/MA were present on both sides of the pelvic peritoneum in EOC patients, with infiltration of the subjacent stroma and mesothelium. CD68+ MO/MA, the most commonly represented population, and CD3+ T cells were present more often in EOC than in benign pelvic tumors. NK cells, B cells, and granulocytes were rare. CXCL8 (IL-8) and the chemokine receptor CCR1 were coexpressed more frequently on MO/MA than on CD3+ cells contrasting with CD68+/CD163+ cells that coexpressed CXCL8 less often. An important activated enzyme in the eicosanoid pathway, pcPLA2, was highly expressed on both CD68+ and CD163+ cells. The adherence molecule Vascular Cell Adhesion Molecule-1 (VCAM1) was expressed on CD31+ endothelial cells and on a proportion of CD68+ MO/MA but rarely on CD3+ cells.ConclusionThe pelvic peritoneum in EOC exhibits a general pattern of chronic inflammation, represented primarily by differentiated MO/MA, and distinct from that in benign conditions concordant with previous profiling results.
Highlights
We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease
We show expression of several of these genes that encode for the following molecules: CXCL8, a contributor to tumor angiogenesis and leukocyte chemotaxis, CD163 the scavenger molecule associated with MA differentiation, CCR1, a chemokine receptor expressed on different leukocytes, including MA and that binds to multiple CC ligands produced by ovarian cancer cells, and MA, Vascular Cell Adhesion Molecule-1 (VCAM1), an adherence moledule and ligand for VLA-4 integrin and induced on endothelial cells by tumor necrosis factor (TNFα), interleukin 1α (IL1α) and certain other cytokines
Our previous gene profile analysis of the EOC peritoneum suggested that CXCL8 (IL-8) has a central role in these inflammatory cell pathways [9,12]
Summary
We previously showed that tumor-free peritoneum of patients with epithelial ovarian cancer (EOC) exhibited enhanced expression of several inflammatory response genes compared to peritoneum of benign disease. We examined peritoneal inflammatory cell patterns to determine their concordance with selected enhanced genes. The peritoneum and its extension, the intestinal serosa, include a vast surface area for transit of inflammatory cells into the abdominal cavity. The peritoneum and intestinal serosa may have a florid appearance similar to that found in peritonitis. Despite this evidence of inflammation, the inflammatory process in the peritoneum of patients with EOC has not been adequately described or characterized
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