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Prostate cancer is the second most common cancer in men worldwide. Prostate Cancer Stem cells have been shown to be responsible for relapse in prostate cancer and the development of Castration Resistant Prostate Cancer (CRPC). As Prostate Cancer Stem cells are not eliminated by traditional drugs, it is important to study them and their interactions to target them with greater efficiency. We isolated Prostate Cancer Stem cells from the PC-3 cell line by treating the cells with 5-Fluorouracil. These stem cells expressed the stem cell markers CD133 and CD44. We showed that Prostate Cancer Stem cells express the chemokine CCL5 and the chemokine receptor CXCR4. These chemokines and receptors were expressed at a significantly higher level by the Prostate Cancer Stem cells in comparison to PC-3 cells. CCL5 and CXCR4 have been shown to be involved in the tumor growth, progression and tumor angiogenesis. We also showed that Prostate Cancer Stem cells express VEGF, c-Src and HIF-1αall of which are involved in tumor angiogenesis. We conclude that Prostate Cancer Stem cells help not only in the resurgence of prostate cancer but also actively participate in the maintenance of the tumor microenvironment. CCL5 could be a potential therapeutic target for Prostate Cancer Stem cells.