Prostate cancer (CaP) is an epithelial malignancy that is a major public health issue in Western industrialized countries, representing the most frequently diagnosed non-skin malignancy cancer in men. Our goal is to utilize the techniques and approaches described above for studies of normal stem cells and cancer stem cells of the skin to better understand and characterize human prostate stem cells (PSC) and human prostate cancer stem cells. We want to determine the relationship of PSC to prostate cancer stem cells, and develop assays to assess the ability of candidate PSC populations to reconstitute the prostate in a mouse model and assess the ability of prostate cancer stem cells to recapitulate prostate cancer in a mouse model.Compared to skin, relatively little is known about the basic biology of prostate epithelial stem cells (PSC), including their precise anatomical location and how the stem cell niche boundaries are defined. PSC have been defined as cells that are able to survive the involution of the prostate and the apoptotic loss of the luminal layer that follows castration or acute androgen withdrawal, and as cells able to reconstitute the luminal layer and regenerate the prostate after androgen restoration. The presence of """"""""intermediate"""""""" cells that contain both basal and luminal cell markers and that may represent transit amplifying cells may support these lineage relationships. However, several recent findings call into question the assumption that PSC are restricted to the basal layer and also raise questions about the lineage relationship between basal cells and luminal cells. Using techniques that we have previously used to characterize the location and lineage relationships of keratinocyte stem cells in the skin, we would like to characterize the anatomical location of PSC in the prostate elucidate the lineage relationships between the basal and luminal cell layers. Another significant problem for characterizing prostate stem cells is the absence of standard in vivo assays to grow and propagate human prostate cancer and normal prostate tissue, a critical requirement for assessing the stem cell behaviors of self-renewal and long-term tissue repopulation. We would like to develop the ability to manipulate cell suspensions derived from either normal human prostate tissue or human prostate cancer in order to reconstitute a normal prostate or recapitulate prostate cancer in an in vivo animal model, analogous to the manipulations that we currently perform with normal skin cells.
