Background The prostate stroma is a key mediator of epithelial differentiation

Background The prostate stroma is a key mediator of epithelial differentiation and development, and potentially plays a role in the initiation and progression of prostate cancer. cell types included that of the CXC-chemokine genes. Conclusion CD90+ prostate tumor-associated stromal cells differed from their normal counterpart in expression of multiple genes, some of which are potentially involved in organ development. Background Prostate stromal mesenchyme fibromuscular cells provide a regulatory extracellular matrix and direct epithelial differentiation and development through growth factors and androgen stimulation [1]. The critical role stromal cells play in prostate development has been demonstrated by co-implantation in animals of stem cells and stromal cells to achieve functional glandular development [2-7]. Although prostate cancer is epithelial in origin, there is a growing body of evidence suggesting that the stromal microenvironment plays a significant role in the cancer process [8-12]. Prostate tumor-associated or ‘reactive’ stroma is characterized by a decrease in smooth muscle cell differentiation and an increase in LY6E antibody myofibroblasts and fibroblasts, with characteristics of a wound repair stroma [13]. Defining the gene expression changes in the stroma of prostate cancer has been the focus of several recent studies and is an important step in defining the underlying mechanisms of stromal-epithelial interaction in cancer. Previous studies have characterized gene expression profiles of tumor-associated stromal cells isolated by laser-capture microdissection (LCM) [14,15] and cultures established from histologically confirmed cancer tissues [16]. These studies have identified genes that are potentially involved in processes such as proliferation and angiogenesis. Current thought is that the tumor-associated stroma always co-exists with cancer [17], and that it may contribute to the gain of metastatic potential by tumor cells and the progression towards androgen-independence [12]. In this study, we sought to identify genes specific to prostate stromal cells that might function in organ specific stromal induction of epithelial development, and to isolate viable stromal cell populations associated with cancer by magnetic cell sorting (MACS) for gene expression analysis and JW-642 IC50 comparison between these cells and their normal counterpart [18-20]. CD90/THY1 is a cell surface molecule expressed in a wide variety of cells including stem and progenitor cells [21-27]. It is thought to be involved in cell recognition, adhesion, and lymphocyte activation [26]. Elevated expression of CD90 has been found in the stromal cells of primary prostate cancer [28]. Previously, CD90hi cells isolated from primary stromal cell cultures of prostate cancer were shown to differentially express several genes associated with tumor-promotion [16]. Here, we used differential expression of CD90 to isolate viable CD90-expressing stromal cells directly from prostate cancer specimens for gene expression profiling and comparison to normal tissue stromal cells. We also used differential expression of CD13 in the bladder stroma to isolate viable CD13-expressing stromal cells from bladder cancer specimens for further comparison. To date there has not been an established marker comparable to CD90 in prostate stroma that differentiates bladder tumor-associated stroma from normal. A population of CD13+ cells in the so-called superficial lamina propria was regarded here as the prostate-equivalent JW-642 IC50 bladder stromal cells because of its proximity to the urothelium [20]. These profiles JW-642 IC50 provide important cell-type specific gene expression data for future in vitro differentiation and development studies to compare cancer-associated and normal tissue stromal cells. We used cell sorting rather than LCM because cell sorting results in a viable population that could subsequently be grown in cell culture whereas LCM cannot. Identification and isolation of a viable, sufficiently pure, cancer-associated stromal cell population from tumor specimens will provide an essential research tool for the study of prostate carcinogenesis. Methods Tissue specimens The methods of tissue collection, expression data generation and analysis used in this study have been published previously [19,29,30]. The tissue samples JW-642 IC50 consisted of prostate tissue specimens obtained from 13 patients undergoing radical prostatectomy under approval by the University of Washington Institutional Review Board. The same approach was used for both cancer-free and cancer-enriched (where at least 85% of the.