| Popis: |
Cadmium (Cd) is a widespread environmental pollutant with several adverse effects on the general population. While Cd is a well-established risk factor for some cancers, such as lung cancer, its impact on prostate cancer (PCa) is not well understood. PCa mortality is associated with its progression to metastatic spread. This underscores the importance of studying the environmental/or molecular factors that govern the progression from organ-confined tumors to widely metastatic disease. To date, most studies addressing the effects of Cd on PCa are focused on the incidence rather than the progression/outcome. Furthermore, most of these epidemiological studies are limited by the small number of samples and the fact that most of these studies measured Cd levels in the air, blood, or urine, which is less applicable for addressing associations in environmental exposure than the measurement of Cd concentrations in the prostate microenvironment. It is still unknown whether Cd is a driver or a consequence of PCa aggressiveness. Addressing the plausibility of causality requires using proper in vitro and in vivo models for sub-micromolar Cd doses that mimic environmental exposure. Most in vitro studies addressing the functional and molecular effects of Cd are limited by the exclusive use of aggressive PCa cell models and very high micromolar unbound Cd concentrations, which are irrelevant for environmental exposure. Significantly, few studies have addressed the effects of sub-micromolar Cd concentrations. Hence, we suggest using nanomolar concentration that resembles real-life exposure, using less aggressive in vitro models such as RWPE-2, employing 3D organoid culture systems, and adopting high throughput-omics techniques, including metallomics, and using transgenic animal models might represent a more effective model. Here, we focus on reports on the impact of Cd on the progression and aggressiveness of already-established PCa instead of on the initial steps of carcinogenesis. We suggest potential future directions for substantiating the plausible link between Cd exposure and PCa aggressiveness. |
