Animal Models of Prostate Cancer

Prostate cancer is now the most common malignancy and the second highest cause of cancer death of men in Western society. It has a reasonably slow doubling time, is initially androgen dependent (AD) or androgen sensitive (AS), produces prostate-specific antigen (PSA), and prostate specific membrane antigen (PSMA) and, with time, metastasizes to lymph nodes, bone, and other organs; it progresses to an androgen-independent (AI) state. Prostate cancer rarely arises spontaneously in animals, and human and animal prostates differ in their anatomy, cellular content, and in the development of spontaneous benign hyper-plasia that commonly occurs in men as they age but rarely in other species. Existing prostate cancer models include rodent models, human cell lines (in the main derived from metastatic deposits), and gene transfer and transgenic models. Only the transgenic models provide the spectrum of disease as it occurs in men, with progression from prostate intraepithelial neoplasia (PIN) through AD to AI disease with metastases. Special systems have been devised to study the growth of prostate cancer cells in bone; these are described elsewhere in this book. The in vivo systems provide the appropriate cellular milieu allowing for epithelial cell-stromal cell interactions that are crucial to the behavior of prostate cancer cells. This chapter provides a critical appraisal of the models and some of their uses in studies of disease progression and for testing new therapeutic options.