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The Angiogenic Activity of Ascites in the Course of Ovarian Cancer as a Marker of Disease Progression

DOI: 10.1155/2014/683757

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Abstract:

Ovarian cancer cells are able to create invasive implants in the peritoneum and their growth is directly associated with the angiogenetic potential. This effect is probably stimulated by vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8), which are both found in ascites. The aim of this study was to assess the influence of ascites produced by ovarian cancer on the angiogenesis. Peritoneal fluid was collected from patients with advanced ovarian cancer; cancer cells were separated from CD45+ leukocytes. Angiogenesis was assessed in mice, after intradermal injection of full cellular suspension together with supernatant or phosphate buffered saline, purified cancer cells suspension, or CD45+ leukocytes suspension. The angiogenesis index (AI) was assessed after 72 hours. VEGF and Il-8 were measured in the supernatant and cellular suspension. AI was the highest in the isolated cancer cells suspensions as well in the group stimulated with supernatant. Both VEGF and IL-8 were high in supernatants from ascites rich in cancer cells (>45%). A significant correlation was revealed between IL-8 concentration and AI. We conclude that ascites in patients with advanced ovarian cancer stimulates angiogenesis and this mechanism is dependent mostly on cancer cells activity and enhanced by cooperation with infiltrating leukocytes. 1. Introduction The ovary is a unique organ as it is characterized by physiological angiogenesis. The development of dominant follicle requires a creation of new vessels, ranging from theca surrounding the follicle. The follicle cells, both thecal and granulose, show proangiogenic activity stimulating the migration and proliferation of endothelial cells [1]. During luteinization, endothelial cells migrate from the theca and form capillaries of the dense vascular network to direct most of the ovarian blood flow toward corpus luteum. The basic proangiogenic factor found in follicle fluid is vascular endothelial growth factor-(VEGF-) stimulated by luteinizing hormone (LH), human chorionic gonadotropin (hCG), and basic fibroblasts growth factor (bFGF), as well as interleukin-8 (IL-8). Their role in an ovary is not only the matter of increased angiogenesis but also the stimulation of proliferation of follicle cells and induction of ovulation by increased permeability of follicle vessels [2]. Pathologic angiogenic activity is the attribute of growing neoplasms, when they reach more than 1-2?mm3 volume. Numerous proangiogenic factors released by solid tumors as well by tumor infiltrating leukocytes have been described so far [3]. There is

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