Prostate Cancer Cells with Stem Cell Characteristics Reconstitute the Original Human Tumor <i>In vivo</i>

TLDR

Cancer may arise from a stem/progenitor cell sharing features with normal tissue, and prostate tumors are classified by Gleason score, a metric not used in current transgenic mouse models. The study aims to develop a model that enhances understanding of human tumor development. The model provides a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and drug resistance. HPET cell lines derived from a prostate cancer specimen reconstitute the original tumor in vivo, differentiate into all three prostate epithelial lineages, express stem and progenitor markers, lack androgen receptor and p63, and serial transplantation demonstrates self‑renewal potential. Cancer Res 2007;67(10):4807–15.

Abstract

Abstract Cancer may arise from a cancer stem/progenitor cell that shares characteristics with its normal counterpart. We report the reconstitution of the original human prostate cancer specimen from epithelial cell lines (termed HPET for human prostate epithelial/hTERT) derived from this sample. These tumors can be described in terms of Gleason score, a classification not applied to any of the transgenic mouse models currently developed to mimic human disease. Immunohistochemical and Western blot analyses indicate that they do not express androgen receptor or p63, similar to that reported for prostate stem cells. These cell lines also express embryonic stem markers (Oct4, Nanog, and Sox2) as well as early progenitor cell markers (CD44 and Nestin) in vitro. Clonally derived HPET cells reconstitute the original human tumor in vivo and differentiate into the three prostate epithelial cell lineages, indicating that they arise from a common stem/progenitor cell. Serial transplantation experiments reconstitute the tumors, suggesting that a fraction of parental or clonally derived HPET cells have self-renewal potential. Thus, this model may enhance our understanding of human tumor development and provide a mechanism for studying cancer stem/progenitor cells in differentiation, tumorigenesis, preclinical testing, and the development of drug resistance. [Cancer Res 2007;67(10):4807–15]