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A System for Studying Epithelial-Stromal Interactions Reveals Distinct Inductive Abilities of Stromal Cells from Benign Prostatic Hyperplasia and Prostate Cancer

Departments of Cancer Biology (W.W.B., S.D.C.), Pathology (R.D.W.), and Urology (M.C.H., S.D.C.), Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157

Address all correspondence and requests for reprints to: Scott D. Cramer, Department of Cancer Biology, Medical Center Boulevard, Winston-Salem, North Carolina 27157. E-mail: scramer{at}wfubmc.edu.

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes, it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone, benign prostatic hyperplasia (BPH-S), and cancer to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone or BPH-1 epithelial cells alone produced no visible grafts. Recombining stromal cells from normal peripheral zone with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized, and sharply demarcated grafts approximately 3–4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining stromal cells from cancer with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye-stained specimens is an efficient method to generate high-quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo, which mimics the natural history of these diseases.

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