Garnering Evidence for the Role of Environmental Cadmium Exposure in Prostate Cancer Progression

Cadmium is an environmental contaminant that poses several health risks. Early epidemiological studies suggested that cadmium was associated with prostate cancer mortality. However, more recent studies showed conflicting evidence. Our hypothesis is that environmental cadmium overburdern can cause an existing cancer to be more aggressive. Most published in vitro studies addressing the association between cadmium and prostate cancer employed very high micromolar concentrations that are not environmentally relevant. In our study, we showed that cadmium at environmentally relevant concentrations resulted in increased PC3 and LAPC4 growth in 3D cultures but not in 2D cultures. We also showed that cadmium is associated with increased migration of PC3 via increased levels of TCTP and PLK1 phosphorylation. Our results also showed that exposure of nude mice with subcutaneous xenografts of LAPC4 to cadmium in drinking water was associated with increased growth of subcutaneous xenografts at 20 ppm dose (1.7 fold). On the contrary, exposure of nude mice with subcutaneous xenografts of PC3 to environmentally relevant cadmium concentrations resulted in decreased tumor volumes at 2 ppm, 5 ppm, and 20 ppm suggesting differential effects of cadmium on tumor models. Transcriptome analysis of LAPC4 xenografts revealed the dysregulation of several targets such as GMPR, RFX3 and CHRNA2. The role of these targets in prostate cancer progression is yet to be understood. However, our results suggest that cadmium at environmentally relevant concentrations increases the aggressiveness of an already existing prostate cancer.