While many of these inflammatory lesions will be resolved naturally without intervention, a subset of these will go on to develop clinical symptoms as a result of chronic inflammation. Furthermore, prostatitis likely effects all men at some point during their life, at least acutely. In fact, greater than 80% of men have evidence of inflammation in their prostate at biopsy. The prostate is subjected to numerous infectious and inflammatory insults over the course of a man's lifetime, ranging from dietary carcinogens to physical trauma to viral and bacterial pathogens. These studies demonstrate that not only are MSCs present in sites of prostate cancer where they may contribute to carcinogenesis, but these cells may also potentially be used to deliver cytotoxic or imaging agents for therapeutic and/or diagnostic purposes. In contrast to primary prostate cancer-derived epithelial cells, fluorescently-labeled PrCSCs & BM-MSCs were both shown to home to CWR22RH prostate cancer xenografts following IV injection. Additionally, like BM-MSCs, these prostate cancer-derived stromal cells (PrCSCs) were shown to differentiate into osteoblasts, adipocytes, & chondrocytes. MSCs in these prostatectomy samples are FAP-, CD90-, CD73-, and CD105-positive, and CD14-, CD20-, CD34-, CD45-, and HLA-DR-negative. Importantly, these analyses were performed on samples prior to expansion in tissue culture. We have demonstrated that MSCs represent 0.01-1.1% of the total cells present in core biopsies from primary human prostatectomies. MSCs are immunoprivileged and have been implicated in tumorigenesis through multiple mechanisms, including promoting proliferation, angiogenesis, and metastasis, in addition to the generation of an immunosuppressive microenvironment. MSCs are minimally defined as plastic-adhering cells characterized by the expression of CD90, CD73, and CD105 in the absence of hematopoietic markers, which can differentiate into osteoblasts, chondrocytes, and adipocytes. Among other cell types, these chemoattractant stimuli recruit BM-MSCs to the tumor. Chronic inflammation is associated with CXCL12, CCL5, and CCL2, which are highly overexpressed in prostate cancer. The prostate is bombarded by numerous infectious & inflammatory insults over a lifetime. Circulating bone marrow-derived Mesenchymal Stem Cells (BM-MSCs) have an innate tropism for tumor tissue in response to the inflammatory microenvironment present in malignant lesions.
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