Metabolic signatures of malignant progression in prostate epithelial cells

Abstract

Prognostic markers that can distinguish indolent from aggressive prostate cancer could have substantial patient benefit, helping to target patients most in need of radical intervention, while avoiding overtreatment of a highly prevalent condition. The search for novel cancer biomarkers has been facilitated by the development of technologies for "global" biomolecular profiling, used in the sciences of transcriptomics, proteomics and metabolic profiling (metabonomics/metabolomics). Using an NMR-based approach we compared intracellular and extracellular metabolic profiles from the immortalised, non-tumourigenic prostate epithelial cell line, RWPE-1 and two tumourigenic sublines with increasing malignant phenotypes, WPE1-NB14 and WPE1-NB11, generated by N-methyl-N-nitrosourea (MNU) mutagenesis. Collectively, these cell lines present an in vitro model of prostate cancer progression and disease aggression. We observed progressive alterations to intracellular levels of multiple metabolites from choline and branched chain amino acid metabolic pathways from RWPE-1 to WPE1-NB14 to WPE1-NB11 cells. In addition specific perturbations to intracellular glycine and lactate and extracellular lactate and alanine were observed relative to the parent line. The pathways implicated by comparative metabolic profiling in this model are known to be altered in human prostate cancer, and potentially represent a source of biomarkers for prostate cancer aggression.