Abstract: The role of tumor cell-host stromal interaction and stromal-specific growth factors in prostate cancer growth, progression and metastasis to the axial skeleton were investigated. Following co-inoculation of athymic mice with human prostate cancer cells (LNCaP) and various nontumorigenic fibroblasts, human prostate-like tumor formation was consistently induced by human bone (MS) fibroblasts (62%), embryonic rat urogenital sinus mesenchymal (rUGM) cells (31%) and Noble rat prostatic fibroblasts (17%), but not by NIH-3T3, normal rat kidney (NRK), or human lung CCD16 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. A novel in vivo method in which a slowly adsorbed matrix (Gelfoam) was employed to deliver concentrated prostate and bone fibroblast-derived conditioned media was also found to induce LNCaP tumor formation in vivo.