Global metabolomics analysis has the potential to uncover novel metabolic pathways that are differentially regulated during
carcinogenesis, aiding in
biomarker discovery for early diagnosis and remission monitoring. Metabolomics studies with human samples can be problematic due to high inter-individual variation; however xenografts of human
cancers in mice offer a well-controlled model system. Urine was collected from a xenograft mouse model of MCF-7
breast cancer and analyzed by mass spectrometry-based metabolomics to identify metabolites associated with
cancer progression. Over 10 weeks, 24 h urine was collected weekly from control mice, mice dosed with
estradiol cypionate (1 mg/mL), mice inoculated with MCF-7 cells (1 × 107) and
estradiol cypionate (1 mg/mL), and mice dosed with MCF-7 cells (1 × 107) only (n = 10/group). Mice that received both
estradiol cypionate and MCF-7 cells developed
tumors from four weeks after inoculation. Five urinary metabolites were identified that were associated with
breast cancer;
enterolactone glucuronide,
coumaric acid sulfate,
capric acid glucuronide, an unknown metabolite, and a novel mammalian metabolite, "taurosebacic
acid". These metabolites revealed a correlation between
tumor growth,
fatty acid synthesis, and potential anti-proliferative effects of gut microbiota-metabolized food derivatives. These
biomarkers may be of value for early diagnosis of
cancer, monitoring of
cancer therapeutics, and may also lead to future mechanistic studies.