Abstract TMIM-070: APELIN PROMOTES OMENTAL METASTASIS OF OVARIAN CANCER CELLS

Abstract

Abstract PURPOSE: Ovarian cancer (OvCa) is mainly metastasized to the peritoneal cavity and omentum, an organ primarily composed of adipocytes. Adipocytes produce adipokines including apelin involved in initiating angiogenesis and promote the initial homing of tumor cells to omentum through adipokine secretion. Apelin and its receptor APJ mediates glucose/energy metabolism and angiogenesis. The study objective is to assess the functional role of apelin/APJ pathway in omental metastasis of OvCa and associated benefits from antagonizing this pathway as a novel treatment strategy against OvCa metastasis. METHODS: Mouse adipocyte cell line 3T3-L1 were used to obtain adipocyte-derived conditioned media (adipo-CM). Apelin concentrations in adipo-CM were quantified using Western blot and ELISA. Migration and invasion of human OvCa cell lines (OVCAR-5APJ and OVCAR-8) were determined in vitro in the presence of adipo-CM. In vivo homing and ex vivo adhesion assays were performed to study the role of apelin/APJ pathway in attracting and attaching APJ-overexpressing OvCa cells to the omentum. RESULTS: Apelin expression was 2.5 fold higher in mature adipocytes compared to that in pre-adipocytes. Mature adipocytes secreted 0.8-1 ng/mL of apelin in the CM. In vivo, high APJ expression increased 'homing-in' of OvCa cells by 2.75-fold to the omentum. Adipo-CM increased transwell migration (3-3.5 fold) and invasion (3.5-4 fold) of OvCa cells in vitro. Adhesion of APJ high expression OvCa cells to mice omentum ex vivo increased by 1.5 fold. These apelin-induced pro-metastatic effects were reversed by apelin-specific antagonist (F13A) in a dose-dependent manner. CONCLUSION: We found that apelin/ APJ pathway potentially promotes OvCa metastasis to omentum and F13A effectively inhibited apelin-induced effects. Citation Format: Samrita Dogra, Deepika Neelakantan, Maulin Mukeshchandra Patel, Beth Griesel, Ann Olson, Florea Lupu, and Sukyung Woo1. APELIN PROMOTES OMENTAL METASTASIS OF OVARIAN CANCER CELLS [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr TMIM-070.