Linking Infection and Prostate Cancer Progression: Toll-like Receptor3 Stimulation Rewires Glucose Metabolism in Prostate Cells.

Background/Aim: The connection between prostate cancer and inflammation has been proposed many years ago, but very little is known about the metabolic adaptations of prostate cells in case of infection or inflammation. The aim of this study was to examine the effect of the stimulation of Toll-like receptor 3 (TLR3) on the metabolism of prostate cancer (PCa) cell lines and benign prostate cells. Materials and Methods: Cytofluorimetry, qRT-PCR, western blot and Gas-chromatography/Mass-spectrometry were used. Results: Reprogramming of glucose utilization involving hypoxiainducible factor 1-alpha (HIF-1 alpha) and the extracellular adenosine axis was observed. TLR3 stimulation synergized with adenosine receptor A2b on PCa cells, and induced a strong production of lactate, exacerbating the Warburg effect. Moreover, stimulation of benign prostate cells with poly I:C reduced lactate secretion, a characteristic typical of the neoplastic transformation. Conclusion: TLR3 stimulation promotes metabolic adaptations likely involved in the mechanisms of disease onset and progression.