Prostate Cancer Stem Cells: A Target for New Therapies
Prostate cancer is now a common disease in men over 50 years of age. Medical therapies for prostate cancer are based on discoveries from the mid-twentieth century, and in the long term are rarely curative. Most treatments are directed towards an androgen receptor-expressing, highly proliferative target cell, which does indeed form the vast majority of cells in a prostate tumour. However, by invoking the existence of a cancer stem cell which, like normal epithelial stem cells in the prostate, does not express androgen receptor and is relatively quiescent, the observed resistance to most medical therapies can be explained. The phenotype of the prostate cancer stem cells is that of a basal cell and cultures derived from cancers, but not benign tissues, express a range of prostate cancer-associated RNAs. Furthermore, stem cells purified on the basis of α2β1 high integrin and CD133 cell surface antigen expression, from an established culture of Gleason 4 (2+2) prostate cancer (P4E6), were able to form multiple intraprostatic tumours in nude mice when grafted orthotopically in a matrigel plug containing human prostatic stroma. The final tumours re-expressed androgen receptor and displayed a histology similar to that of a Gleason 4 cancer.
KeywordsProstate Cancer Androgen Receptor Cancer Stem Cell Stem Cell Population Luminal Cell
We wish to thank Yorkshire Cancer Research and the National Cancer Research Institute for their continuing support of this work. Professors Freddy Hamdy and Nikki Brown (University of Sheffield) provided valuable and expert assistance in the xenograft technique, and Caty Hyde and Paul Berry processed the primary tissues and maintained the long-term cultures.
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