Abstract 6116: Role of secretory factors from obese-derived omentum in supporting ovarian cancer progression

Abstract

Abstract Ovarian cancer is the most lethal gynecological malignancy in the United States, with a known predilection for metastasizing to the omentum, a sheet of fatty peritoneal tissue that encloses the abdomen. This finding coincides with some evidence that ovarian cancer is more aggressive in the obese setting with worse overall survival. While it has been shown that ovarian cancer cells invade towards adipocytes in vitro, the mechanism by which they support formation of secondary tumors is not well understood. We hypothesize that soluble factors enriched in the obese setting are activating signaling pathways in tumor cells to drive migration and proliferation. To evaluate this hypothesis we co-cultured primary human omental adipocytes derived from obese female donors with ovarian cancer cell lines and profiled secretory factors (cytokines and adipokines) responsible for increasing tumor initiation in vivo and clonogenicity, proliferation, and drug resistance in vitro. Secretion of cytokines IL-6, IL-8, and CCL2 by adipocytes is enhanced when co-cultured with ovarian cancer cells. A subcutaneous tumor model showed that low dilutions of ovarian cancer cells require adipocytes for engraftment and tumor formation. A transplantation assay showed that ovarian cancer cells require the presence of adipocytes for sustained tumor-initiation capacity. Studies are underway to investigate adipocyte-secreted factors in this process. Our findings highlight the role of adipocytes in the ovarian tumor microenvironment and uncover signaling factors that may enhance ovarian cancer progression. Understanding these processes will enable the design of more effective therapies for treating ovarian cancer. Citation Format: Jennifer Waters, Mikella Robinson, Samuel F. Gilbert, Logan J. Alexander, Carrie D. House. Role of secretory factors from obese-derived omentum in supporting ovarian cancer progression [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6116.