Tributyltin-dysregulated periprostatic adipose tissue enhances prostate cell survival and migration, implicating the C-C motif chemokine receptor 3.

Obesity-dysregulated periprostatic adipose tissue (PPAT) has been implicated in the aggressiveness of prostate cancer (PCa). On the other hand, obesity has been linked to environmental influences, namely, the endocrine-disrupting chemicals capable of promoting adipogenesis and fat accumulation (obesogens). However, it is unknown whether obesogens can induce PPAT dysfunction, disrupting its crosstalk with PCa cells. The present study hypothesises that obesogens can target the PPAT, affecting its secretory activity and contributing to the development or aggressiveness of PCa. Through in vivo, ex vivo approaches and conditioned medium (CM) assays, we demonstrated that exposure to tributyltin (TBT), the first described obesogen, induced a PPAT "obese" phenotype, with adipocyte enlargement and enhanced secretion of leptin and C-C motif chemokine ligand 7 (CCL7). TBT-PPAT altered prostate cell fate, enhancing their viability, proliferation and migration, and reducing apoptotic rate. Moreover, it was shown that the TBT-PPAT secretome promoted the migration of prostate cells involving the C-C motif chemokine receptor 3 (CCR3). Overall, this study demonstrated the biological significance of TBT exposure, bringing functional evidence on the contribution of PPAT obesogenic dysregulation to prostate carcinogenesis. Moreover, it highlights the differences that may exist in PCa monitoring and treatment in obese vs. lean patients, pointing out the modulation of PPAT activity as a therapeutic target.