Abstract 808: Aggregation alters the metabolism of serous ovarian cancer cells

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 may increase survival of cancer and metastasis to other tissues. We have previously reported metabolic changes in adherent ovarian cancer cells to rely more heavily on glycolysis. However, metabolic changes in cancer cell aggregates are poorly understood. In this study, we investigated differences in spheroid metabolism in normoxic and hypoxic conditions as compared to adherent cells. We examined late-stage and tumor-initiating murine ovarian cancer monolayers and spheroids. Using a Seahorse XF extracellular flux analyzer, we investigated changes in metabolism over time in the presence of mitochondrial inhibitors (oligomycin and rotenone) or uncouplers (FCCP). Data show a reduction in basal respiration, maximal oxygen consumption rate, and spare respiratory capacity of spheroids compared to adherent monolayers. This suggests a reduction in energetic demand and metabolic flexibility in spheroids, which may confer increased survival capabilities. The identification of these metabolic changes that may increase survival and metastasis of spheroids provide targets for treatment to control the ability of spheroids to survive in the peritoneal cavity. Citation Format: Stephanie Edwards, Emily Pyne, Lu Lui, Jack Guinan, Madlyn Frisard, Eva Schmelz. Aggregation alters the metabolism of serous ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 808.