Abstract 2405: Metabolic plasticity of ovarian metastases in response to adherence and physiologically relevant culture conditions

Abstract

Abstract Ovarian cancer is typically diagnosed at late stages with a poor prognosis due to high recurrence. Exfoliation from the primary tumor results in aggregation of ovarian cancer cells into spheroids in the peritoneal cavity, which then adhere to secondary sites to form metastatic outgrowth. Spheroids in the peritoneal cavity are exposed to hypoxic, low glucose conditions. Sphingosine-1-phosphate (S1P), increased in the ascites fluid of ovarian cancer patients, has been shown to increase tumor cell survival and tumorigenesis through changes in mitochondrial function. However, little is known about these effects in ovarian cancer spheroids, particularly upon secondary adherence and outgrowth in physiological conditions. Changes in spheroid metabolism in response to treatment with S1P, hypoxia, low glucose, and obese peritoneal serous fluid (PSF) in both free and adherent states was investigated. Using a late-stage and tumor-initiating murine ovarian cancer model, spheroids were subjected to treatment with S1P or obese PSF as free or adherent spheroids. Using a Seahorse XFe96, we investigated changes in metabolism over time trials measured after 24 hour treatment for free spheroids and after different time points of adherence (4, 8, 12, and 24 hours). Data show changes in basal respiration, maximal oxygen consumption rate, and spare respiratory capacity of spheroids over adherence time when treated with S1P and PSF. This suggests that the cells respond to energetic demand with metabolic flexibility as the spheroids adhere to new surfaces. The identification of the regulation of these events may help elucidate the flexibility that takes place during metastasis in culture that more closely mimics physiological conditions, providing a foundation for future interventions for preventative therapies for ovarian cancer with dietary sphingolipids and possible treatment targets. Citation Format: Stephanie Edwards Compton, Joseph Grieco, Eva M. Schmelz. Metabolic plasticity of ovarian metastases in response to adherence and physiologically relevant culture conditions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2405.