Metabolic Profiling of Breast Cancer Cell Lines: Unique and Shared Metabolites

Breast Cancer (BrCa) exhibits a high phenotypic heterogeneity, leading to the emergence of aggressive clones and the development of drug resistance. Considering the BrCa heterogeneity and that metabolic reprogramming is a cancer hallmark, we selected seven BrCa cell lines with diverse subtypes to provide their comprehensive metabolome characterization: five lines commonly used (SK-Br-3, T-47D, MCF-7, MDA-MB-436, and MDA-MB-231), and two patient-derived xenografts (Hbcx39 and Hbcx9). We characterized their endometabolomes using ¹H-NMR spectroscopy. We found distinct metabolite profiles, with certain metabolites being common but differentially accumulated across the selected BrCa cell lines. High levels of glycine, lactate, glutamate, and formate, metabolites known to promote invasion and metastasis, were detected in all BrCa cells. In our experiment setting were identified unique metabolites to specific cell lines: xanthine and 2-oxoglutarate in SK-Br-3, 2-oxobutyrate in T-47D, cystathionine and glucose-1-phosphate in MCF-7, NAD⁺ in MDA-MB-436, isocitrate in MDA-MB-231, and NADP⁺ in Hbcx9. The unique and enriched metabolites enabled us to identify the metabolic pathways modulated in a cell-line-specific manner, which may represent potential candidate targets for therapeutic intervention. We believe this study may contribute to the functional characterization of BrCa cells and assist in selecting appropriate cell lines for drug-response studies.