Abstract
Abstract Metabolism in cancer cells is significantly altered as compared to their normal counterparts. Metabolic rewiring can assist cancer cells to meet their requirements for uncontrolled proliferation and survival. In addition to their role in protein synthesis and energy generation, metabolites also act as signaling molecules, antioxidants and perform osmoregulatory functions. Differences in genetic makeup and phenotype of cells can lead to differences in these metabolic needs. A detailed analysis of metabolic signatures of different cancer cells can therefore prove useful in understanding metabolic interactions with the phenotype in cancer cells. This study aims at identifying these metabolic differences among distinct breast cancer cell lines and gaining mechanistic insights into possible reasons for differential abundance of metabolites. We used nuclear magnetic resonance (NMR) spectroscopy to quantify intracellular metabolites in five breast cancer cell lines having distinct genetic and phenotypic composition. We show that the intracellular abundance of essential amino acids depends on cell type and medium composition. We also show that myo-inositol abundance was significantly higher in ER-/PR- than ER+/PR+ breast cancer cells due to increased expression of inositol-3-phosphate synthase 1 expression. Myo-inositol is an osmolyte and also a precursor of inositol phosphates which participate in PI3K and calcium signaling pathways. Although the reason ER-/PR- cells contain greater concentrations of myo-inositol than ER+/PR+ cells is not yet known, increased myo-inositol abundance could potentially serve as a marker of ER-/PR- breast cancer cells. We also observed significant changes in phospholipid metabolism, specifically, glycerophosohocholine (GPC) concentration correlated with doubling time. We also found that reducing serum concentration in the growth medium reduced the growth rate of MCF7 cells, which led to increased GPC abundance in the cells. GPC is also an intracellular osmolyte and is a degradation product of phosphatidylcholine (PtdCho). Phospholipid metabolism has been shown to be significantly altered in breast cancer cells and has been used as prognostic marker in breast cancer cells. A positive correlation of doubling time with GPC irrespective of ER/PR status may prove useful in deciding therapeutic options. Our results highlight the differences in metabolic requirements in different breast cancer cell lines and suggest potential for gaining mechanistic understanding of these differences using metabolomics. Note: This abstract was not presented at the meeting. Citation Format: Vijesh J. Bhute, Kylie R. Knutson, Yan Ma, Sean P. Palecek. Differential metabolite requirements in breast cancer cells correlate with ER/PR status and doubling time [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2520. doi:10.1158/1538-7445.AM2017-2520
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