부산대학교 도서관

In prostate cancer research, there is a lack of valuable preclinical models. Tumor cell heterogeneity and sensitivity to microenvironment signals, such as hypoxia or extracellular calcium concentration, are difficult to reproduce. Here, we developed and characterized an ex vivotissue culture model preserving these properties. Prostate tissue slices from 26 patients were maintained ex vivounder optimized culture conditions. The expression of markers associated with proliferation, androgen-receptor signaling, and hypoxia was assessed by immunostaining. A Macro Zoom System Microscope was used to achieve real-time calcium fluorescence optical imaging. Tissue morphology was maintained successfully without necrosis for 5 days. Compared with native tumors and tissue cultured with androgens, androgen deprivation in the medium led to decreased expression of both androgen receptor and its target gene products, PSA and ERG. Ex vivocultured slices also were sensitive to hypoxia because carbonic anhydrase IX and Zeb1 protein levels increased in 1% oxygen. Exposure of slices to supraphysiological extracellular Ca2+concentration induced a robust and rapid Ca2+entry, with a greater response in tumor compared with nontumor tissue. This ex vivomodel reproduces the morphologic and functional characteristics of human prostate cancer, including sensitivity to androgen deprivation and induced response to hypoxia and extracellular Ca2+. It therefore could become an attractive tool for drug response prediction studies.