Research Trends and Regulation of CCL5 in Prostate Cancer

Figures & data

Figure 1 The role of CCL5 in PCa. CCL5 promotes PCa proliferation, angiogenesis, metastasis, the formation of stem cells and drug resistance via the crosslinking with CCR5 or CCR1.

Table 1 The Therapeutic Effect of Drugs on the Action of CCL5/CCR5 Axis in Prostate Cancer

Name	Characteristics	Effects of Anti-Prostate Cancer	References
Maraviroc	CCR5 Antagonist. IC50 of CCR5 is 5.2 nM.	1.Reduced the rate of brain metastasis and bone metastasis in vivo.	[^Citation66,Citation83,Citation84]
Cenicriviroc (also known as TAK-799)	1.CCR5 and CCR2 Antagonist. 2.IC50 of CCR5 is 1.4 nM.	1.Inhibition of tumor proliferation and migration in vitro.	[^Citation21,Citation76]
Anibamine	1.CCR5 Antagonist. 2.IC50 of CCR5 is 1.0 μM.	1.Inhibition of tumor proliferation and migration in vitro. 2.provides a structural skeleton of chemical modification of CCR5 antagonist in vitro.	[^Citation85^–^Citation88]
DT-13	1.CCR5 Antagonist. 2.IC50 of CCR5 is 1.0μM.	1.Inhibition of tumor proliferation, angiogenesis and migration in vitro. 2.Synergistically enhance the effect of chemotherapeutics in vitro.	[^Citation81,Citation90^–^Citation93]

Figure 2 Model of the regions of the human CCL5 promoter. The regions A to E and G named in order of discovery and their base sequence and binding transcription factor were summarized. The percentages below each region demonstrate the percentage of CCL5 promoter activity remaining after deleting that region.

Abbreviations: NFAT, nuclear factor of activated T cells; PU.1/Ets-1, Ets family members; ATF3, activating transcription factor 3; JunD/FosB/Fra1/Fra2, AP1 family members; R(C)FLAT, R(C) factor of late activated T cells; HMG(γ), high-mobility group protein (γ); IRF-1, interferon regulatory factor-1; GABP, GA binding protein; NF-IL6, nuclear factor of interleukin 6; C/EBP, CAAT/enhancer binding protein; SPBP, stromelysin-1 PDGF responsive element binding protein; NF-ƙB, nuclear factor kappa B; p50/p50, NF-ƙB p50 subunit homodimer; p50/p65, NF-ƙB Rel family members; R(A)FLAT-1, R(A) factor of late activated T cells-1; Sp1, stimulating protein 1.

Figure 3 The transcription factor regulating CCL5 predicted by analysing the UCSC database. We firstly found the base sequence −2000 bp to 100 bp from the CCL5 transcriptional start point and then predicted the transcription factor with the base sequence through using the PROMO database with 5% fault tolerance.

Abbreviations: TBP, TATA-binding protein; TFIID, general transcription factor; PITX2, paired-liked homeodo-main transcription factor 2; TCF-4, T cell factor 4; VDR, vitamin D receptor; XBP-1, X-box binding protein-1; YY1, YIN-YANG 1; IK-1, IKaros-1; PR, progesterone receptor; P53, tumor suppressor gene; FOX, Forkhead box; C/EBP, CAAT/enhancer binding protein; AP-2, integrase-type DNA-binding superfamily protein; AR, androgen receptor; Jun/Fos, AP1 family members; Ets-1/Ets-2, Ets family members; C-Myb, MYB proto-oncogene; ER, Leucine-rich receptor-like protein kinase family protein; GATA, Glutamyl-tRNA amidotransferase, subunit A; GR, glutathione reductase; HNF-1A/HNF-1B/HNF-1C, HNF1 homeobox family members; IRF-1, interferon regulatory factor-1; LEF-1, lymphoid enhancer binding factor 1; NF-1, nuclear factor-1; NF-AT, nuclear factor of activated T cells; NF1/CTF, nuclear factor 1 family of site-specific DNA-binding proteins; NF-Y, nuclear factor-Y; Pax-5, paired box 5; PEA3, polymoma virus enhancer 3; PPAR, peroxisome proliferator-activated receptor; PXR/RAR/RXR, nuclear receptor; RelA, RELA proto-oncogene, NF-kB subunit; Sp1, stimulating protein 1; STAT, signal transducer and activator of transcription; T3R-β1, thyroid hormone receptor-beta 1.

Figure 4 The schematic diagram of the downstream pathways of CCL5 in PCa. (A) The human umbilical vein endothelial cells (HUVECs), bone stromal cells, macrophages and cancer-associated fibroblasts (CAF) can promote PCa cell metastasis by secreting CCL5 in tumor microenvironment. (B) By secreting CCL5, bone marrow mesenchymal stem cells (BM-MSCs) promote PCa metastasis and stemness. (C) By secreting CCL5, PCa recruit mast cells which can release FGF-2, VEGF and IL-6 to promote angiogenesis. (D) CCL5 promotes the proliferation of prostate cancer. (E) CCL5 promotes the drug resistance of prostate cancer.

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