Summary:
Bladder cancer is the most common urological malignancy. Early diagnosis of bladder cancer is crucial to improve patient outcomes. Currently, metabolomics is a potential technique that can be used to detect bladder cancer.
Plasticity and reprogramming of cellular metabolism have proved to act as strong forces in tumorigenesis. Malignant hallmarks, such as cell survival under stress conditions, as well as the ability to utilize nutrients and successfully encounter high-energy demands, are tightly correlated with metabolic alterations, thus indicating the important roles of metabolic landscapes in Cancer Biology and therapy. Metabolic activities may significantly differ between different malignancy stages (grades) of the same type of cancer, leading to distinct metabolic networks and metabolomes. In this study, we present a comparative NMR- and LC-MS/MS-mediated untargeted metabolic profiling of human urothelial bladder cancer (hUBC) to landscape the metabolic alterations tumor cells are subjected during cancer progression, while we also discuss methodological issues on the metabolomic analysis herein performed.
The metabolic landscapes of grade 1 to grade 4 human urinary bladder cancer cell lines were extensively investigated, using four different cell lines; the RT4 (grade 1), RT112 (grade 2), T24 (grade 3) and TCCSUP (grade 4) ones (10 individual samples from each cell line were examined). The obtained results unveiled diverse and malignancy-grade -specific metabolite collections, critically implicated in amino acid metabolism, tricarboxylic acid (TCA) cycle and energy metabolism, as well as purine and pyrimidine metabolism. A small, but significant, increase was observed in Grade 2 (RT112) compared to grade 1 (RT4) cells, while grade 3 (T24) cells proved to carry surprisingly upregulated levels of most metabolites, with the amino acid metabolic network being emerged as a powerful and promising novel platform for bladder cancer targeted therapy. However, in TCCSUP (grade 4) cells, the levels of most identified metabolites, including those involved in amino acid metabolism, were notably reduced compared to RT112 (grade 2) and T24 (grade 3) cell-line respective ones, likely indicating a “metabolic inversion” of the cellular machinery during late metastasis.
Keywords:
Metabolomics, "metabolic inversion", NMR, MS
