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Unraveling the metabolome in prostate tumorigenesis: Effects by an oncogenic isopeptidase.

e16148 Background: Cancer cells undergo fundamental changes in their metabolism, including a higher rate of glycolysis and an increase in de novo fatty acid synthesis. The high incorporation of glucose into tumor cells has already been exploited in cancer diagnostics with the generation of the FDG-PET scan technology. However, some tumors including those arising in the prostate are less prone to FDG-PET imaging and could benefit from other imaging techniques based on alternative metabolic features. We asked whether prostate epithelial cell transformation driven by specific oncogenes results in a typical metabolic profiling, whose characterization may be useful to improve diagnostics and to address new therapeutics.


METHODS
Normal prostate epithelial cells (RWPE-1 and PrEC) were transformed by overexpressing known oncogenes, such as the protein kinase AKT1 and the de-ubiquitinating enzyme (isopeptidase) USP2a. These cells were then subjected to mass spectrometry-based metabolomics, gene expression analysis, oxygen consumption and glucose uptake assays. Multiple bioinformatic tools were utilized for data mining and pathway visualization.


RESULTS
We integrated data from different high-throughput technologies to map metabolic changes induced during prostate tumorigenesis by genes that are often altered in prostate cancer. A different metabolic profiling was found in association to each specific oncogene. In fact, extremely significant alterations were found in the glycolytic pathways in the case of AKT-driven transformation, whereas changes in the lipid metabolism and in some aminoacids were prevalent in USP2a-overexpressing cells. Complementary assays including oxygen consumption and glucose uptake measurement confirmed the global metabolic analysis.


CONCLUSIONS
These results suggest that tumors showing different genetic alterations may be characterized by a different metabolic profiling, whose assessment can potentially improve diagnostics and individualized treatment. Metabolic profiling analysis of human prostate tumors is currently ongoing. No significant financial relationships to disclose.