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A model of human prostate cancer was established to study cellular interaction between prostate cancer and bone stroma in vivo. In this model, subcutaneous co‐injection of 2 non‐tumorigenic human cell lines‐LNCaP, a prostate cancer cell line, and MS, a bone stromal cell line‐into intact adult male mice resulted in formation of carcinomas that secreted prostate‐specific antigen (PSA), a clinically useful human serum prostate cancer marker. In castrated hosts, upon cellular interaction with bone fibroblasts, we observed the progression of these tumors from an androgen‐dependent (AD) to an androgen‐independent state (AI). We derived 4 LNCaP cell sublines from the chimeric LNCaP/MS tumors: the M subline from intact hosts and the C4, C4‐2 and C5 sublines from castrated hosts. The LNCaP sublines had chromosomal markers similar to those of the parental LNCaP cells and distinctly different from those of …