Bisphenol A Alters the Energy Metabolism of Stromal Cells and Could Promote Bladder Cancer Progression

SIMPLE SUMMARY: Our research brings new insight on the potential impact of bisphenol A on bladder cancer progression. By evaluating the effects of bisphenol A on the stromal environment of bladder cancer, we aimed to demonstrate that this endocrine disruptor could promote bladder cancer invasion through alteration of the energy metabolism of stromal cells, specifically on bladder fibroblasts and cancer-associated fibroblasts. These findings could modify the understanding of bladder cancer since bladder tissue is not recognized as a hormone-sensitive tissue. Consequently, our study suggests that endocrine disruptors, such as bisphenol A, could impact bladder cancer progression. ABSTRACT: Bisphenol A (BPA) is an endocrine-disrupting molecule used in plastics. Through its release in food and the environment, BPA can be found in humans and is mostly excreted in urine. The bladder is therefore continuously exposed to this compound. BPA can bind to multiple cell receptors involved in proliferation, migration and invasion pathways, and exposure to BPA is associated with cancer progression. Considering the physiological concentrations of BPA in urine, we tested the effect of nanomolar concentrations of BPA on the metabolism of bladder fibroblasts and cancer-associated fibroblasts (CAFs). Our results show that BPA led to a decreased metabolism in fibroblasts, which could alter the extracellular matrix. Furthermore, CAF induction triggered a metabolic switch, similar to the Warburg effect described in cancer cells. Additionally, we demonstrated that nanomolar concentrations of BPA could exacerbate this metabolic switch observed in CAFs via an increased glycolytic metabolism, leading to greater acidification of the extracellular environment. These findings suggest that chronic exposure to BPA could promote cancer progression through an alteration of the metabolism of stromal cells.