Abstract 981: Study of altered metabolism due to anoikis resistance in ovarian cancer

Abstract Cancer cells have recently been shown to be resistant to anoikis, a form of cell death due to detachment, thus decreasing responsiveness to therapy. Catecholamines, antioxidants, and oncogenes have been shown to rescue metabolic defects caused during cell detachment. Thus, there is a strong motivation to study metabolic alterations associated with anoikis resistance in cancer. Despite efforts to understand the link between anoikis and cancer metabolism, extensive metabolic analysis of cancer cells is lacking. Tissue engineering of cancer cells to create three-dimensional cell environments can also be used as a model system to study cancer metabolism. We postulate that anoikis can be regulated by metabolism in tissue engineered cultures of ovarian cancer (OC) cells. Our findings using quantification of metabolites by conducting Ultra Performance Liquid Chromatography and metabolic assays pertaining to central carbon and nitrogen metabolism provided clues as to which pathways relevant to glycolysis, the pentose phosphate pathway, the TCA and urea cycles, lipid cycle, and amino acid and nucleotide metabolisms, may be altered by anoxia in cancer cells, resulting in identification of dominant factors which regulate OC metabolism. Amino acid supplementation significantly increased the TCA cycle flux at the level of citrate synthase and the fatty acid-derived acetyl-CoA to CO2. The information we have gained elucidates the critical role of metabolism in anoikis resistance in OCC in tissue engineered cultures. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 981. doi:10.1158/1538-7445.AM2011-981