Molecular Characterization of Cancer Associated Fibroblasts in Prostate Cancer

SIMPLE SUMMARY: Primary, organ-confined prostate cancer is treatable with surgery, chemotherapy, radiation, and active surveillance; however, a subset of patients will develop metastatic disease. The main issue in prostate cancer is the need of prognostic tools for identifying patients at risk for lethal metastatic tumor, as well as a lack of curative therapies for such patients. The tissues surrounding the prostate cancer cells consist of a mixture of stromal cells that are structurally and functionally different from stromal cells in normal prostate. The stromal component, as a source of prognostic information for metastatic disease progression, has received little attention. In the present study, we characterized stromal cells from cancer tissues as compared to stromal cells from normal adjacent tumor tissue or human benign prostate. The stroma’s specific profile will allow to predict the presence of aggressive tumors, therapy resistance, and metastasis development. ABSTRACT: Background: Stromal components surrounding epithelial cancer cells seem to play a pivotal role during epithelial-to-mesenchymal transition (EMT), tumor invasion, and metastases. To identify the molecular mechanisms underlying tumor–stroma interactions may yield novel therapeutic targets for prostate cancer. Methods: Gene expression profile of prostate-cancer associated fibroblast (PCAF) and prostate non-cancer associated fibroblast (PNAF) cells isolated from radical prostatectomy was performed by Illumina, analyzed, and further processed by Ingenuity(®): IPA(®) software. qRT-PCR was performed on an independent set of 17 PCAF, 12 PNAF, and 12 fibroblast cell lines derived from patients with benign prostatic hyperplasia (BPHF). Results: Using microarray analysis, we found six upregulated genes and two downregulated genes in PCAFs compared to PNAFs. To validate microarray results, we performed qRT-PCR for the most significantly regulated genes involved in the modulation of proliferation and androgen resistance on an independent set of PNAF, PCAF, and BHPF samples. We confirmed the increased expression of SCARB1, MAPK3K1, and TGF-β as well as the decreased expression of S100A10 in PCAFs compared to PNAFs and BPHFs. Conclusions: These results provide strong evidence that the observed changes in the gene expression profile of PCAFs can contribute to functional alteration of adjacent prostate cancer cells.