EXPRESSION OF CHEMOKINE (C-C MOTIF) RECEPTOR 7 IN PROSTATE CANCER TISSUE OF YOUNG PATIENTS AND IN METASTATIC CANCER CELLS
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-44-no-2.18025Keywords:
CCR-7, chemokine, early onset, prostate cancerAbstract
Background: Chemokine (C-C motif) receptor 7 (CCR7) is a chemokine receptor involved in the carcinogenesis of several types of tumors due to its promoting action in epithelial-mesenchymal transition events, invasion, angiogenesis and metastasis. However, its role in prostate cancer (PCa) remains unclear. Aim: To evaluate CCR7 expression by immunohistochemistry in prostate tumors from young patients and to determine the possible relationship with the clinicopathological characteristics. Materials and Methods: We analyzed retrospectively paraffin-embedded tissue sections from 23 young PCa (≤ 55 years old) patients and evaluated the transcriptomic expression in the TCGA database. Results: Expression of CCR7 was observed in 15 cases (65%). The tissue samples from younger patients (≤ 50 years) were mostly positive in 72.7% (8/11) of cases. High grade GS (≥ 3) tumors were CCR7-positive in 71% cases. The malignant cells present in lymph nodes were CCR7 positive in 100% cases. The bioinformatic analysis showed a high CCR7 expression associated with the presence of metastasis (FC = 2.6, p = 0.03) in the Cancer Genome Atlas (TCGA) PCa cohort (PRAD). Conclusion: We showed that CCR7 expression in tumors from young patients is associated with the early onset of the disease and could also be related to lymph node metastasis.
References
Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209–49. https://doi.org/10.3322/caac.21660
Zheng Y, Lin SX, Wu S, et al. Clinicopathological characteristics of localized prostate cancer in younger men aged ≤ 50 years treated with radical prostatectomy in the PSA era: A systematic review and meta-analysis. Cancer Med 2020; 9: 6473–84. https://doi.org/10.1002/cam4.3320
Parra-medina R, Ramírez-Clavijo S. Cáncer de próstata de inicio temprano. ¿ Una nueva entidad ? Rev Mex Urol 2021; 81: 1–13.
Hussein S, Satturwar S, Van der Kwast T. Young-age prostate cancer. J Clin Pathol 2015; 68: 511–5. https://doi.org/10.1136/jclinpath- 2015-202993
Lange EM, Salinas CA, Zuhlke KA, et al. Early onset prostate cancer has a significant genetic component. Prostate 2012; 72: 147–56. https://doi.org/10.1002/pros.21414
Leongamornlert DA, Saunders EJ, Wakerell S, et al. Germline DNA repair gene mutations in young-onset prostate cancer cases in the UK: Evidence for a more extensive genetic panel. Eur Urol 2019; 76: 329–37. https://doi.org/10.1016/j.eururo.2019.01.050
Lange EM, Johnson AM, Wang Y, et al. Genome-wide association scan for variants associated with early-onset prostate cancer. PLoS One 2014; 9: e93436. https://doi.org/10.1371/journal.pone.0093436
Weischenfeldt J, Simon R, Feuerbach L, et al. Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer. Cancer Cell 2013; 23: 159–70. https://doi.org/10.1016/j.ccr.2013.01.002
Hanahan D. Hallmarks of cancer: new dimensions. Cancer Discov 2022; 12: 31-46. https://doi.org/10.1016/j.cell.2011.02.013
Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol 2015; 7: a016303. https://doi.org/10.1101/cshperspect.a016303
Rani A, Dasgupta P, Murphy JJ. Prostate cancer: the role of inflammation and chemokines. Am J Pathol 2019; 189: 2119–37. https://doi.org/10.1016/j.ajpath.2019.07.007
Ding Y, Wu H, Warden C, et al. Gene expression differences in prostate cancers between young and old men. PLOS Genet 2016; 12: e1006477. https://doi.org/10.1371/journal.pgen.1006477
Parra-Medina R, López-Kleine L, Ramírez-Clavijo S, et al. Identification of candidate miRNAs in early-onset and late-onset prostate cancer by network analysis. Sci Rep 2020; 10: 1–14. https://doi.org/10.1038/s41598-020-69290-7
Valera VA, Parra-Medina R, Walter BA, et al. microRNA expression profiling in young prostate cancer patients. J Cancer 2020; 11: 4106–14. https://doi.org/10.7150/jca.37842
Hirao M, Onai N, Hiroishi K, et al. CC chemokine receptor-7 on dendritic cells is induced after interaction with apoptotic tumor cells: critical role in migration from the tumor site to draining lymph nodes. Cancer Res 2000; 60: 2209–17.
Korbecki J, Grochans S, Gutowska I, et al. CC chemokines in a tumor: a review of pro-cancer and anti-cancer properties of receptors CCR5, CCR6, CCR7, CCR8, CCR9, and CCR10 ligands. Int J Mol Sci 2020; 21: 7619. https://doi.org/10.3390/ijms21207619
Salem A, Alotaibi M, Mroueh R, et al. CCR7 as a therapeutic target in Cancer. Biochim Biophys Acta Rev Cancer 2021; 1875: 188499. https://doi.org/10.1016/j.bbcan.2020.188499
Zu G, Luo B, Yang Y, et al. Meta-analysis of the prognostic value of C-C chemokine receptor type 7 in patients with solid tumors. Cancer Manag Res 2019; 11: 1881–92. https://doi.org/10.2147/CMAR.S190510
Du R, Tang G, Tang Z, et al. Ectopic expression of CC chemokine receptor 7 promotes prostate cancer cells metastasis via Notch1 signaling. J Cell Biochem 2019; 120: 9639–47. https://doi.org/10.1002/jcb.28242
Maolake A, Izumi K, Natsagdorj A, et al. Tumor necrosis factor-α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation. Cancer Sci 2018; 109: 1524–31. https://doi.org/10.1111/cas.13586
Zheng L, Dou X, Ma X, et al. Identification of potential key genes and pathways in enzalutamide-resistant prostate cancer cell lines: a bioinformatics analysis with data from the gene expression omnibus (GEO) database. Biomed Res Int 2020; 2020: 8341097. https://doi.org/10.1155/2020/8341097
Collado-Torres L, Nellore A, Kammers K, et al. Reproducible RNA-seq analysis using recount2. Nat Biotechnol 2017; 35: 319–21. https://doi.org/10.1038/nbt.3838
Afgan E, Baker D, van den Beek M, et al. The Galaxy platform for accessible, reproducible and collaborative biomedical analyses: 2016 update. Nucleic Acids Res 2016; 44: W3–10. https://doi.org/10.1093/nar/gkw343
Coussens LM, Zitvogel L, Palucka AK. Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science 2013; 339: 286–91. https://doi.org/10.1126/science.1232227
Rizeq B, Malki MI. The Role of CCL21/CCR7 chemokine axis in breast cancer progression. Cancers 2020; 12: 1036. https://doi.org/10.3390/cancers12041036
Chi B-J, Du C-L, Fu Y-F, et al. Silencing of CCR7 inhibits the growth, invasion and migration of prostate cancer cells induced by VEGFC. Int J Clin Exp Pathol 2015; 8: 12533–40.
Youlin K, Weiyang H, Simin L, et al. Prostaglandin E 2 inhibits prostate cancer progression by countervailing tumor microenvironment-induced impairment of dendritic cell migration through LXR α /CCR7 pathway. J Immunol Res 2018; 2018: 1–8. https://doi.org/10.1155/2018/5808962
Rodríguez-Berriguete G, Fraile B, Martínez-Onsurbe P, et al. MAP kinases and prostate cancer. J Signal Transduct 2012; 2012: 1–9. https://doi.org/10.1155/2012/169170
Dong Z, Bonfil RD, Chinni S, et al. Matrix metalloproteinase activity and osteoclasts in experimental prostate cancer bone metastasis tissue. Am J Pathol 2005; 166: 1173–86. https://doi.org/10.1016/S0002-9440(10)62337-1
Rankin EB, Nam J-M, Giaccia AJ. Hypoxia: signaling the metastatic cascade. Trends Cancer 2016; 2: 295–304. https://doi.org/10.1016/j.trecan.2016.05.006
Li M, Wang YX, Luo Y, et al. Hypoxia inducible factor-1α-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells. Oncol Rep 2016; 36: 521–7. https://doi.org/10.3892/or.2016.4766
Palayoor ST, Mitchell JB, Cerna D, et al. PX-478, an inhibitor of hypoxia-inducible factor-1alpha, enhances radiosensitivity of prostate carcinoma cells. Int J Cancer 2008; 123: 2430–7. https://doi.org/10.1002/ijc.23807
Rudolfsson SH, Bergh A. Hypoxia drives prostate tumour progression and impairs the effectiveness of therapy, but can also promote cell death and serve as a therapeutic target. Expert Opin Ther Targets 2009; 13: 219–25. https://doi.org/10.1517/14728220802626249
Pipinikas CP, Carter ND, Corbishley CM, et al. HIF-1α mRNA gene expression levels in improved diagnosis of early stages of prostate cancer. Biomarkers 2008; 13: 680–91. https://doi.org/10.1080/13547500802591992
Xiao L-J, Chen Y-Y, Lin P, et al. Hypoxia increases CX3CR1 expression via HIF-1 and NF-κB in androgen-independent prostate cancer cells. Int J Oncol 2012; 41: 1827–36. https://doi.org/10.3892/ijo.2012.1610
Wilson JL, Burchell J, Grimshaw MJ. Endothelins induce CCR7 expression by breast tumor cells via endothelin receptor A and hypoxia-inducible factor-1. Cancer Res 2006; 66: 11802–7. https://doi.org/10.1158/0008-5472.CAN-06-1222
Li Y, Qiu X, Zhang S, et al. Hypoxia-induced CCR7 expression via HIF-1α and HIF-2α correlates with migration and invasion in lung cancer cells. Cancer Biol Ther 2009; 8: 322–30. https://doi.org/10.4161/cbt.8.4.7332
Basheer HA, Pakanavicius E, Cooper PA, et al. Hypoxia modulates CCR7 expression in head and neck cancers. Oral Oncol 2018; 80: 64–73. https://doi.org/10.1016/j.oraloncology.2018.03.014
Cheng S, Han L, Guo J, et al. The essential roles of CCR7 in epithelial-to-mesenchymal transition induced by hypoxia in epithelial ovarian carcinomas. Tumor Biol 2014; 35: 12293–8. https://doi.org/10.1007/s13277-014-2540-6
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