BioProject

Prostate cancer (PCa) is heterogeneous containing both phenotypically differentiated and undifferentiated tumor cells. More...

Prostate cancer (PCa) is heterogeneous containing both phenotypically differentiated and undifferentiated tumor cells. An important unanswered question is whether these two populations of PCa cells are functionally different. Here we report the distinct molecular, cellular, and tumor-propagating properties of PCa cells that express high (i.e., PSA+) and low (PSA-/lo) levels of the differentiation marker PSA (prostatespecific antigen). PSA-/lo PCa cells are quiescent and resistant to multiple stresses including androgen deprivation, exhibit high clonogenic potential, and possess long-term tumor-propagating capacity in male mice. They preferentially express stem cell-associated genes and can undergo asymmetric cell division generating PSA+ cells. Importantly, PSA-/lo PCa cells can initiate robust tumor development in castrated hosts, survive androgen deprivation, and harbor highly tumorigenic castration-resistant PCa cells that can be further enriched using the ALDH+CD44+α2β1+ phenotype. In contrast, PSA+ PCa cells possess more limited tumor-propagating capacity, mainly undergo symmetric division, and are sensitive to castration. Together, our study suggests that PSA-/lo and PSA+ PCa cells are functionally distinct and PSA-/lo cells may represent one critical source of castration-resistant PCa cells. Overall design: There are 4 sets of human samples in this study corresponding to 4 different prostate cancer patients labeled as HPCa46T, HPCa47T, HPCa49T and HPCa51T. Each set includes 3 technical triplicates (except HPCa46T) that were performed on dual color arrays and each individual array includes comparisons between PSA- (Cy5) and PSA+ (Cy3) cells of the respective patient prostate tumor. Less...