Androgen‐insensitive prostate cancer cells transiently respond to castration treatment when growing in an androgen‐dependent prostate environment

Abstract

BACKGROUND Castration-induced involution of the normal prostate is caused by primary effects in the prostate stroma and vasculature, but if this is the case also in tumors is unknown. METHODS Androgen-independent AT-1 prostate tumor cells were therefore injected into the ventral prostate (VP) in Copenhagen rats. Seven days later when the growing tumor was surrounded by normal VP tissue the rats were castrated and the effect examined 3 and 7 days later. RESULTS Castration reduced vascular density in the surrounding VP tissue and this was accompanied by tumor cell hypoxia, apoptosis, and temporarily retarded tumor growth. Castration-induced VP tissue regression occurred more rapidly in the contra-lateral than in the tumor-bearing lobe. CONCLUSIONS Androgen-independent tumor cell respond to castration when growing in an androgen-dependent environment. The presence of a tumor influences the castration response in the surrounding normal tissue. The microenvironment determines how prostate epithelial cells respond to castration. Prostate 67: 370–377, 2007.