Omental Fat In Ovarian Cancer Potentially Induces Lymphangiogenesis

Background Ovarian cancer metastasis occurs by direct multifocal seeding in the peritoneum as well as by migration through the lymphatic system. High grade ovarian carcinoma patients present with distant metastases. Significant risk factors for the development of those are stage, grade, and lymph node involvement. An increase of the number of lymphatic vessels is shown in ovarian tumors and these vessels seem implicated in tumor progression. While the tropism of ovarian cancer cells for fat is well described, the potential impact of a fatty microenvironment on the dissemination of tumor cells via lymphatic vessels has, to our knowledge, never been investigated yet. In this study, we examined the effect of omental fat on lymphangiogenesis in ovarian carcinoma. Materials and Methods To examine the effect of omental fat on lymphangiogenesis in OC we used a cohort of 80 human specimens. We analysed lymphatic vessels histologically with D2-40 and Lyve-1 markers. We also developed a healthy fat tissue explant culture model and treated explants with ascites of patient with OC before analysis. We analysed by fluorescence stainings the co expression of adipose derived stem cells (ASCs) and lymphatic markers in these explants. Results We observed a higher density of tumor-associated vessels, especially lymphatic vessels in OC in contact with the omentum; mainly localized along the adipose tissue. We also measured a higher secretion of VEGF-C in tissues with fat compared to tissues without fat. Healthy fat tissues treated with ascites show an increase of number of ASCs, some of them express lymphatic markers such as D2-40 and Lyve-1. In a clinical trial of patients with OC treated by Bevacizumab, we observed a decrease of the number of lymphatic vessels in correlation with a decrease of the inflammation around the fat tissue. Discussion We saw an increase in the number of lymphatic vessels in ovarian carcinoma infiltrating fat. These vessels are principally distributed around the fat. We also observed an increase of proliferating ASC expressing lymphatic marker in fat explants treated with ascites. In a clinical trial of patients treated with Bevacizumab, we see a decrease of the lymphatic vessels. This decrease is linked with a decrease in the number of Inflammatory cells. These results together show that the fat tissue can play an important role in the lymphangiogenesis in the ovarian carcinoma. Furthermore, in the dissemination of metastasis through the body. We will next investigate the mechanisms underlying this phenomenon and try to understand all factors implicated in this process. Disclosure Information B.M.A. Lenoir: None. V. Starrach: None. D. Ferber: None. M. Suarez-Carmona: None. S. Schott: None. I. Zornig: None. D. Jager: None. N. Halama: None.