**7. Concluding Remarks**

Our recent studies have elucidated several CCL-CCR axes involved in prostate cancer progression, some of which are negatively regulated by androgen/AR signaling and vice versa (Figure 1). Other CCL-CCR axes may play significant roles in prostate cancer progression, while CCL-CCR axes form chemokine-networks in which CCL-CCR axes are capable of activating and/or inactivating one another. In summary, the complete elucidation of this chemokine-network, including the exact function of each chemokine, is required to control prostate cancer cells across every stage.

**Figure 1.** Androgen receptor (AR) and C-C motif ligand (CCL)-receptor (CCR) axes. (1) Androgen/AR signaling negatively regulates CCL2 secretion and inhibits prostate cancer cell migration. The CCL2-CCR2 axis contributes to chemoresistance to taxanes. (2) The CCL22-CCR4 axis is located downstream of the CCL2-CCR2 axis and increases the migratory capacity of prostate cancer cells. (3) CCL5 activity occurs upstream of AR signaling and increases the migratory capacity of prostate cancer cells via inhibition of androgen/AR signaling. (4) CCL4 is positively regulated by androgen/AR signaling in macrophages, and is a key regulator during prostate tumorigenesis. (5) TNF, which is negatively regulated by androgen/AR signaling, induces CCR7 expression in prostate cancer cells. CCR7 subsequently binds CCL21 from fibroblastic reticular cells in lymph node, resulting in increased migratory capacity.

**Author Contributions:** K.I. wrote the manuscript. A.M. revised the manuscript. **Conflicts of Interest:** The authors declare no conflict of interest.
