Normal prostate-derived stromal cells stimulate prostate cancer development.

Stromal cells play a decisive role in regulating tumor progression. In this study, we assessed the significance of normal prostate-derived stromal cells (PSCs) in prostate cancer development. An in vivo s.c. tumor model was established as follows: Group 1, DU145 cells alone; Group 2, DU145 + PSCs; Group 3, DU145 cells alone injected into pre-castrated mice; and Group 4, DU145 + PSCs injected into pre-castrated mice. Following injection, tumors were only detectable in the first two groups, with more aggressive growth in Group 2 than in Group 1 (P < 0.05). Immunohistochemical analysis revealed significantly higher proliferation (P < 0.05), but not apoptosis or altered expression of androgen receptor in Group 2, as compared with Group 1. In vitro, DU145 cells isolated from Group 1 tumors showed lower viability and migratory capability than those from Group 2. cDNA microarray on isolated DU145 cells from Groups 1 and 2 revealed the differential expression of genes regulating cell cycle progression and cell mobility, including GADD45A, RHOV, KLK11, and PCK1. Our results suggest that stromal cells derived from normal prostate potentiate the development of tumor growth in vivo, which is achieved at least in part through the regulation of cell-cycle- and migration-related gene expression within the tumor cells.