Abstract 3481: Elucidating the metabolic crosstalk between lymphatic endothelial cells and breast cancer using 1H NMR metabolomics

Abstract

Abstract Breast cancer is the second most commonly diagnosed cancer among women worldwide. Patient death is typically caused by metastasis development rather than the primary tumor. Metastasis in breast cancer has been shown to occur via blood and lymphatic vessels. Research shows that breast cancer cells ‘educate' lymphatic and blood endothelial cells to support tumor growth by stimulating growth factor secretion and directing tumor dissemination. In addition, cell metabolism is altered during malignant transformation. Cancer cells have increased energy and macromolecule biosynthesis requirements to sustain rapid proliferation. However, it remains unclear how tumor endothelial cell metabolism is altered and how metabolism contributes to tumor metastasis. Therefore, this study aims to use 1H NMR metabolomics to identify breast cancer-endothelial cell metabolic interactions in a high-throughput manner. Firstly, we studied if in vitro co-culture with breast cancer altered endothelial cell metabolism. We identified distinct metabolic profiles for lymphatic endothelial cells (LECs) grown in monoculture or co-culture with three different breast cancer cell lines. Principal component analysis revealed LECs co-cultured with breast cancer cells clustered separately from control LECs. Interestingly, LECs co-cultured with triple negative breast cancer cells clustered together with LECs co-cultured with HER2+ breast cancer cell lines indicating that the metabolic changes occurring in these LECs were similar. One-way ANOVA with Tukey's HSD post-hoc analysis revealed 17 significantly different metabolites between all five conditions analyzed including: lactate, glucose, phosphocholine, aspartate, acetate, glycerophosphocholine, lysine and methionine. Quantitative metabolite set enrichment analysis revealed 13 metabolic pathways that were significantly enriched between control LECs and LECs co-cultured with breast cancer cell lines. Enriched pathways included: glycolysis, gluconeogenesis, pyruvate metabolism and protein biosynthesis. Together, these results indicate that culturing LECs with certain breast cancer lines causes significant changes in endothelial metabolism. Alterations in endothelial cell metabolism in response to breast cancer co-culture can further our understanding of tumor-vascular interactions and may lead to identification of metabolic biomarkers and a better understanding of breast cancer metastasis. Citation Format: Suehelay Acevedo-Acevedo, Douglas C. Millar, Sean P. Palecek. Elucidating the metabolic crosstalk between lymphatic endothelial cells and breast cancer using 1H NMR metabolomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3481.