Using H-1 Nmr Metabolomics To Study Breast Cancer And Endothelial Cell Metabolic Interactions

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; specifically VEGF, PDGF-BB and EGF secretion. In addition, cell metabolism is altered during malignant transformation. Cancer cells have increased energy and macromolecule biosynthesis requirements to sustain rapid proliferation. Increased angiogenesis observed in tumors points to a need for an increased nutrient supply. However, it remains unclear how tumor endothelial cell metabolism is altered and how metabolism regulates tumor angiogenesis. 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 HUVECs grown in monoculture or co-culture with three different breast cancer cell lines. Metabolism of HUVECs co-cultured with MCF7 and SKBR3 breast cancer cell lines was significantly altered compared to mono-culture control. The most impacted metabolic pathways by co-culture were amino acid metabolism, energy metabolism and lipid biosynthesis pathways. Culturing HUVECs with MDA-MB-231 triple negative breast cancer cells did not have a significant impact on HUVEC metabolism, however. Together, these results indicate that culturing HUVECs 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 or therapeutic targets that can disrupt tumor angiogenesis. Citation Format: Suehelay Acevedo-Acevedo, Sean P. Palecek. Using 1 H NMR metabolomics to study breast cancer and endothelial cell metabolic interactions [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 2507. doi:10.1158/1538-7445.AM2017-2507