Temporal expression profiling of the effects of secreted factors from prostate stromal cells on embryonal carcinoma stem cells

BACKGROUND There is a growing body of evidence indicating that epigenetic influences originating from stromal cells in the immediate microenvironment may play a role in carcinogenesis. Determining the molecular mechanisms involved in stromal–stem cell interaction could provide critical insight into prostate development and disease progression, particularly with regard to their relationship to and influence on the putative cancer stem cell. METHODS Prostate and bladder stromal cells prepared from tissue specimens were co-cultured with the pluripotent embryonal carcinoma cell line NCCIT. Transcriptome analysis was used to characterize NCCIT cell response to prostate or bladder signaling. RESULTS A systems approach demonstrated that prostate stromal cells were capable of inducing gene expression changes in NCCIT through secreted factors. Induction led to a loss of embryonic stem cell markers, with concurrent up-regulation of many genes characteristic of stromal mesenchyme cells as well as some of epithelial and cancer stem cells. Bladder stromal signaling produced gene expression changes different from those of prostate signaling. CONCLUSIONS This study indicates that paracrine stromal cell signaling can affect cancer stem cell response in an organ-specific manner and may provide insight for future development of treatment strategies such as differentiation therapy. Prostate 69:1353–1365, 2009. © 2009 Wiley-Liss, Inc.