Androgen Deprivation Alters the Transcriptome of Endothelial Cells More Dramatically in Human Prostate Cancer Tissue than in Benign Prostate Tissue

Purpose: Examine the cell type specific (Epithelial, Endothelial, and Stromal) transcriptome profile between prostate primary tissue xenografts of prostate tissue tumor tissue and uninvolved tissue (named non-tumor hereafter) in response testosterone (T) deprivation. Additional cell type specific untreated fresh tissue from both tumor and non-tumor samples is included for additional validation. Related samples previously uploaded to GEO are found under accession number GSE145641. Method: Nude-Fox1nu mice were castrated and silastic tubing containing dry T was inserted providing “humanized” levels of circulating T. 5-8 pieces of fresh human prostate tissue was then inserted subcutaneously along the flank of the animal. For samples not subjected to T-deprivation, after 30 days the animal was euthanized, and tissue was harvested. For samples undergoing T-deprivation, after 30 days with humanized circulating T levels, T-deprivation was performed by surgical removal of silastic tubing after which serum T levels dropped below the level of detection within 24 hours. Samples were then harvested at Pre T-deprivation time point, an early T-deprivation time point (3-days) or late T-deprivation timepoint (15-17 days) post-surgery. Tissue from fresh human prostate or tissue from xenograft and was then enriched into endothelial, epithelial and the remaining stromal compartments using magnetic bead enrichment. RNA-Seq was then preformed on cell types from both origins and the results compared to determine the cell type specific effects of T-deprivation on the human prostate transcriptome.