Effects of cadmium on proliferation and self-renewal activity of prostate stem/progenitor cells

Cadmium (Cd) is an occupational and environmental pollutant that induces numerous pathological effects, including injuries to prostate. The aim of the present study was to investigate the effects of Cd on self-renewal and proliferation of prostate stem/progenitor cells (PSPC) and its possible mechanisms. Prostate epithelial cells were prepared from mice to form sphere in Matrigel/PrEGM supplemented with cadmium chloride (CdCl2). The data showed that CdCl2 inhibits sphere-forming ability and proliferation of PSPC in a concentration dependent manner. Primary spheres were then passaged to form daughter spheres and we found that CdCl2 suppressed PSPC self-renewal activity, which recovered after further passaging. We also detected the protein level of androgen receptor (AR) in the spheres of each passage. The results showed that AR in primary spheres is suppressed by CdCl2 in a concentration dependent manner. However, no obvious change of AR was found in subsequent passages. The in vivo toxicity of CdCl2 on PSPC was detected by giving mice drinking water with CdCl2. Our results demonstrated in vivo inhibition effect of CdCl2 on self-renewal activity of PSPC. Consistent with in vitro results, self-renewal activity of PSPC was recovered after CdCl2 withdrawal. In addition, CdCl2 also in vivo suppressed PSPC proliferation as indicated by Ki67 immunostaining. Our finding suggested that Cd may inhibit proliferation and self-renewal activity of PSPC by suppressing AR, which could be important to further understanding the complex mechanism of Cd toxicity in prostate.

► Cd inhibits sphere-forming ability and proliferation of PSPC in cell culture in a concentration dependent manner.
► Cd in vitro suppresses PSPC self-renewal activity, which recovers after further passaging.
► Androgen receptor is suppressed by Cd in a concentration dependent manner.
► Cd in vivo inhibits PSPC self-renewal activity, which recovers after Cd withdrawal.
► Cd in vivo suppresses PSPC proliferation as indicated by Ki67 immunostaining.