Human Stromal Cells in the Peripheral Zone of the Prostate Promote Tumorigenesis of Prostatic Cancer Stem Cells through Up-regulation of C-Kit Expression

Objective: Most prostate cancers originate from the prostatic peripheral zone (PZ). We tested the hypothesis that the stromal cells from PZ and transitional zone (TZ) have differential effects on the ability of tumorigenesis. Methods: Stromal cells isolated from the PZ and TZ of normal human prostates mixed with DU145 cells subcutaneously injected into athymic nude mice. The volume and weight of tumors was measured and analyzing the ability of purified DU145 cells isolated from the tumors to migrate and proliferate. The expression patterns of stem cell-specific genes of these DU145 cells were examined. The C-Kit inhibitor, imatinib mesylate, was administrated to confirm the effect of stromal cells on the tumorigenesis. Results: The volume and weight of tumors were significantly higher in mice transplanted with DU145 and stromal cells from PZ. In contrast, the data was significantly lower with DU145 and stromal cells from TZ than DU145 alone. The purified DU145 cells isolated from the tumors with DU145 and stromal cells in PZ had increased ability to migrate and proliferate, and had increased expression of C-Kit. These effects of the stromal cells in the PZ on DU145 cells could be blocked using imatinib mesylate. Conclusions: Human stromal cells in the PZ promote the in vivo tumorigenesis of DU145 through up-regulating C-Kit; in contrast, the stromal cells in the TZ inhibit it through down-regulating the expression of C-Kit. The model will be useful for understanding the mechanisms by which the prostatic stem cell niche controls the tumorigeneis of prostatic cancer stem cells.