Hierarchical organization of prostate cancer (PCa) cells

1025

The concept that tumors contain stem-like cells or cancer stem cells (CSCs) is supported by increasing experimental evidence and accepted by increasing numbers of scientists and clinical investigators. Tumor-initiating, presumptive CSCs have now been identified not only in hematopoietic cancers but also in several solid tumors including breast and brain tumors. Our lab, in the past several years, has focused on prostate cancer (PCa) and identified several populations of tumorigenic PCa cells including the Side Population (SP), α2β1hi, CD44+, and ABCG2+ cells. These cells appear to mark a spectrum of tumorigenic PCa cells from potential long-term CSCs (i.e., SP), to short-term CSCs (i.e., CD44), and to highly proliferative tumor progenitor (or transit amplifying) cells (i.e., the α2β1hi and ABCG2+) (Cancer Res. 65, 6207, 2005; Oncogene, 2005, in press). We have also utilized genetically defined approaches to immortalize normal human prostate epithelial stem/progenitor cells that maintain tripotential differentiation abilities in vivo. Our short-term goals are to find ways that can allow us to capture most tumorigenic cells in PCa and to establish a potential developmental hierarchy of various populations of PCa stem and progenitor cells. Our intermediate goal is to compare the gene and protein expression profiles of prostate CSCs with those of normal prostate stem/progenitor cells. Our long-term goal is to utilize the unique gene/protein expression signatures of prostate CSCs, combined with our expertise on apoptosis, to develop novel therapeutics specifically targeting the rare but important tumorigenic cells.