Metabolic fingerprinting of breast cancer cell lines: discovering similarities and differences

Metabolic fingerprinting of breast cancer cell lines: discovering similarities and differences. Metabolic rewiring is one of the hallmarks of cancer. The metabolic reprogramming process is complex and influenced by multiple factors. It depends on the type and specific features of tumours. This study aimed to create a database of the metabolomes of selected breast cancer (BrCa) cell lines derived from tumour subtypes with different aggressiveness and to identify shared and unique features to understand the metabolic reprogramming of BrCa better. We selected five cell lines commonly used for in vitro studies, including MCF-7 and T-47D (luminal A), SK-Br-3 (HER2+), and MDA-MB-436 and MDA-MB-231 (triple negative), and two patient-derived xenografts Hbcx9 and Hcbx39 (triple negative). We used 1H-NMR spectroscopy to obtain the intracellular polar metabolic profiles of these BrCa cells cultured in optimal growth conditions. The seven cell lines exhibit distinct metabolomes, reflecting the heterogeneity of BrCa tumours. Using enriched metabolites, we identified cell-specific activated metabolic pathways. Remarkably, for the four triple negative cells, different pathways are preferentially activated: inositol phosphate metabolism in Hbcx9, purine metabolism in Hbcx39, the Krebs cycle and pyrimidine metabolism in MDA-MB-231, and nicotinate and niacinamide metabolism in MDA-MB-436. Since all patients with triple-negative tumours usually receive standardised chemotherapy, this finding may provide a prospective insight towards developing more personalised therapies. In addition, despite the metabolic differences, some metabolites can be associated with the current tumour subtype classification and aggressiveness. Finally, we compared known metabolic adaptive features of cancer within the cell lines. This study provides a database of the intracellular metabolite profiles of selected BrCa cell lines that can be useful for future research studies. It also uncovered specific features that may be helpful in the discovery of new therapeutic targets.