Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
June-2017 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2017 Volume 13 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review

Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review)

  • Authors:
    • Zhiwei Zhao
    • Shichao Wang
    • Yingbo Lin
    • Yali Miao
    • Ye Zeng
    • Yongmei Nie
    • Peng Guo
    • Guangyao Jiang
    • Jiang Wu
  • View Affiliations / Copyright

    Affiliations: West China Medical Center, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Oncology and Pathology, Karolinska Institute, Cancer Centre Karolinska, SE‑171 76 Stockholm, Sweden, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, School of Basic Medicine, Xinjiang Medical University, Urumqi, Xinjiang 830011, P.R. China, Outpatient Building, West China Fourth Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China
  • Pages: 4577-4584
    |
    Published online on: April 13, 2017
       https://doi.org/10.3892/ol.2017.6034
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Epithelial-mesenchymal transition (EMT) is a biological process that is associated with cancer metastasis and invasion. In cancer, EMT promotes cell motility, invasion and distant metastasis. Interleukin (IL)-8 is highly expressed in tumors and may induce EMT. The IL‑8/IL‑8R axis has a vital role in EMT in carcinoma, which is regulated by several signaling pathways, including the transforming growth factor β‑spleen associated tyrosine kinase/Src-AKT/extracellular signal‑regulated kinase, p38/Jun N‑terminal kinase‑activating transcription factor‑2, phosphoinositide 3-kinase/AKT, nuclear factor-κB and Wnt signaling pathways. Blocking the IL‑8/IL‑8R signaling pathway may be a novel strategy to reduce metastasis and improve patient survival rates. This review will cover IL‑8‑IL‑8R signaling pathway in tumor epithelial-mesenchymal transition.
View Figures

Figure 1

View References

1 

Lee K and Nelson CM: New insights into the regulation of epithelial-mesenchymal transition and tissue fibrosis. Int Rev Cell Mol Biol. 294:171–221. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Desai S, Laskar S and Pandey BN: Autocrine IL-8 and VEGF mediate epithelial-mesenchymal transition and invasiveness via p38/JNK-ATF-2 signalling in A549 lung cancer cells. Cell Signal. 25:1780–1791. 2013. View Article : Google Scholar : PubMed/NCBI

3 

Nieto MA: The ins and outs of the epithelial to mesenchymal transition in health and disease. Annu Rev Cell Dev Biol. 27:347–376. 2011. View Article : Google Scholar : PubMed/NCBI

4 

Li XJ, Peng LX, Shao JY, Lu WH, Zhang JX, Chen S, Chen ZY, Xiang YQ, Bao YN, Zheng FJ, et al: As an independent unfavorable prognostic factor, IL-8 promotes metastasis of nasopharyngeal carcinoma through induction of epithelial-mesenchymal transition and activation of AKT signaling. Carcinogenesis. 33:1302–1309. 2012. View Article : Google Scholar : PubMed/NCBI

5 

Mathias RA, Gopal SK and Simpson RJ: Contribution of cells undergoing epithelial-mesenchymal transition to the tumour microenvironment. J Proteomics. 78:545–57. 2013. View Article : Google Scholar : PubMed/NCBI

6 

Palena C, Hamilton DH and Fernando RI: Influence of IL-8 on the epithelial-mesenchymal transition and the tumor microenvironment. Future Oncol. 8:713–722. 2012. View Article : Google Scholar : PubMed/NCBI

7 

Malmberg KJ and Ljunggren HG: Escape from immune- and nonimmune-mediated tumor surveillance. Semin Cancer Biol. 16:16–31. 2006. View Article : Google Scholar : PubMed/NCBI

8 

Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG and Strieter RM: Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science. 258:1798–1801. 1992. View Article : Google Scholar : PubMed/NCBI

9 

Bhusari PA and Khairnar KB: Greater omental pancake tumour due to metastasis of ovarian cancer-a cadaveric study. J Clin Diagn Res. 8:142–143. 2014.PubMed/NCBI

10 

Yu J, Ren X, Chen Y, Liu P, Wei X, Li H, Ying G, Chen K, Winkler H and Hao X: Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients. PLoS One. 8:e560692013. View Article : Google Scholar : PubMed/NCBI

11 

Fernando RI, Castillo MD, Litzinger M, Hamilton DH and Palena C: IL-8 signaling plays a critical role in the epithelial-mesenchymal transition of human carcinoma cells. Cancer Res. 71:5296–5306. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Islam SS, Mokhtari RB, El Hout Y, Azadi MA, Alauddin M, Yeger H and Farhat WA: TGF-β1 induces EMT reprogramming of porcine bladder urothelial cells into collagen producing fibroblasts-like cells in a Smad2/Smad3-dependent manner. J Cell Commun Signal. 8:39–58. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Bose SK, Meyer K, Di Bisceglie AM, Ray RB and Ray R: Hepatitis C virus induces epithelial-mesenchymal transition in primary human hepatocytes. J Virol. 86:13621–13628. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, et al: Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature. 436:123–127. 2005. View Article : Google Scholar : PubMed/NCBI

15 

Ye Y, Liu P, Wang Y, Li H, Wei F, Cheng Y, Han L and Yu J: Neurotensin, a novel messenger to cross-link inflammation and tumor invasion via epithelial-mesenchymal transition pathway. Int Rev Immunol. 35:340–350. 2016.PubMed/NCBI

16 

Zhou N, Lu F, Liu C, Xu K, Huang J, Yu D and Bi L: IL-8 induces the epithelial-mesenchymal transition of renal cell carcinoma cells through the activation of AKT signaling. Oncol Lett. 12:1915–1920. 2016.PubMed/NCBI

17 

Nieto MA: Epithelial plasticity: A common theme in embryonic and cancer cells. Science. 342:12348502013. View Article : Google Scholar : PubMed/NCBI

18 

Hugo H, Ackland ML, Blick T, Lawrence MG, Clements JA, Williams ED and Thompson EW: Epithelial-mesenchymal and mesenchymal-epithelial transitions in carcinoma progression. J Cell Physiol. 213:374–383. 2007. View Article : Google Scholar : PubMed/NCBI

19 

Thiery JP, Acloque H, Huang RY and Nieto MA: Epithelial-mesenchymal transitions in development and disease. Cell. 139:871–890. 2009. View Article : Google Scholar : PubMed/NCBI

20 

Kim MJ, Doh II, Bae GY, Cha HJ and Cho YH: Cell-matrix adhesion characterization using multiple shear stress zones in single stepwise microchannel. Appl Phys Lett. 105:0837012016. View Article : Google Scholar

21 

Rokavec M, Öner MG, Li H, Jackstadt R, Jiang L, Lodygin D, Kaller M, Horst D, Ziegler PK, Schwitalla S, et al: IL-6R/STAT3/miR-34a feedback loop promotes EMT-mediated colorectal cancer invasion and metastasis. J Clin Invest. 124:1853–1867. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Berx G, Raspé E, Christofori G, Thiery JP and Sleeman JP: Pre-EMTing metastasis? Recapitulation of morphogenetic processes in cancer. Clin Exp Metastasis. 24:587–597. 2007. View Article : Google Scholar : PubMed/NCBI

23 

Yang J and Weinberg RA: Epithelial-mesenchymal transition: At the crossroads of development and tumor metastasis. Dev Cell. 14:818–829. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Ota I, Li XY, Hu Y and Weiss SJ: Induction of a MT1-MMP and MT2-MMP-dependent basement membrane transmigration program in cancer cells by Snail1. Proc Natl Acad Sci USA. 106:pp. 20318–20323. 2009; View Article : Google Scholar : PubMed/NCBI

25 

Sarrio D, Rodriguez-Pinilla SM, Hardisson D, Cano A, Moreno-Bueno G and Palacios J: Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype. Cancer Res. 68:989–997. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Desai S, Kumar A, Laskar S and Pandey BN: Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells. Cytokine. 61:54–62. 2013. View Article : Google Scholar : PubMed/NCBI

27 

Dudley AT, Lyons KM and Robertson EJ: A requirement for bone morphogenetic protein-7 during development of the mammalian kidney and eye. Genes Dev. 9:2795–2807. 1995. View Article : Google Scholar : PubMed/NCBI

28 

Illman SA, Lehti K, Keski-Oja J and Lohi J: Epilysin (MMP-28) induces TGF-beta mediated epithelial to mesenchymal transition in lung carcinoma cells. J Cell Science. 119:3856–3865. 2006. View Article : Google Scholar : PubMed/NCBI

29 

Xiong M, Jiang L, Zhou Y, Qiu W, Fang L, Tan R, Wen P and Yang J: The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression. Am J Physiol Renal Physiol. 302:F369–F379. 2012. View Article : Google Scholar : PubMed/NCBI

30 

Park GB, Kim D, Kim YS, Kim S, Lee HK, Yang JW and Hur DY: The Epstein-Barr virus causes epithelial-mesenchymal transition in human corneal epithelial cells via Syk/src and Akt/Erk signaling pathways. Invest Ophthalmol Vis Sci. 55:1770–1779. 2014. View Article : Google Scholar : PubMed/NCBI

31 

Guo CB, Wang S, Deng C, Zhang DL, Wang FL and Jin XQ: Relationship between matrix metalloproteinase 2 and lung cancer progression. Mol Diagn Ther. 11:183–192. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Gregory AD and Houghton AM: Tumor-associated neutrophils: New targets for cancer therapy. Cancer Res. 71:2411–2416. 2011. View Article : Google Scholar : PubMed/NCBI

33 

Fang S, Yu L, Mei H, Yang J, Gao T, Cheng A, Guo W, Xia K and Liu G: Cisplatin promotes mesenchymal-like characteristics in osteosarcoma through Snail. Oncol Lett. 12:5007–5014. 2016.PubMed/NCBI

34 

Alba-Castellon L, Olivera-Salguero R, Mestre-Farrera A, Pena R, Herrera M, Bonilla F, Casal JI, Baulida J, Peña C and García de Herreros A: Snail1-dependent activation of cancer-associated fibroblast controls epithelial tumor cell invasion and metastasis. Cancer Res. 76:6205–6217. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Haraguchi M, Sato M and Ozawa M: CRISPR/Cas9n-mediated deletion of the Snail 1Gene (SNAI1) reveals its role in regulating cell morphology, cell-cell interactions and gene expression in ovarian cancer (RMG-1) cells. PLoS One. 10:e01322602015. View Article : Google Scholar : PubMed/NCBI

36 

Hwang WL, Yang MH, Tsai ML, Lan HY, Su SH, Chang SC, Teng HW, Yang SH, Lan YT, Chiou SH and Wang HW: SNAIL regulates interleukin-8 expression, stem cell-like activity and tumorigenicity of human colorectal carcinoma cells. Gastroenterology. 141:279–291, 291.e1-e5. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Leong KG, Niessen K, Kulic I, Raouf A, Eaves C, Pollet I and Karsan A: Jagged1-mediated Notch activation induces epithelial-to-mesenchymal transition through Slug-induced repression of E-cadherin. J Exp Med. 204:2935–2948. 2007. View Article : Google Scholar : PubMed/NCBI

38 

Niessen K, Fu Y, Chang L, Hoodless PA, McFadden D and Karsan A: Slug is a direct Notch target required for initiation of cardiac cushion cellularization. J Cell Biol. 182:315–325. 2008. View Article : Google Scholar : PubMed/NCBI

39 

Sahlgren C, Gustafsson MV, Jin S, Poellinger L and Lendahl UL: Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA. 105:pp. 6392–6397. 2008; View Article : Google Scholar : PubMed/NCBI

40 

Timmerman LA, Grego-Bessa J, Raya A, Bertrén E, Pérez-Pomares JM, Díez J, Aranda S, Palomo S, McCormick F, Izpisúa-Belmonte JC and de la Pompa JL: Notch promotes epithelial-mesenchymal transition during cardiac development and oncogenic transformation. Genes Dev. 18:99–115. 2004. View Article : Google Scholar : PubMed/NCBI

41 

Yanagawa J, Walser TC, Zhu LX, Hong L, Fishbein MC, Mah V, Chia D, Goodglick L, Elashoff DA, Luo J, et al: Snail promotes CXCR2 ligand-dependent tumor progression in non-small cell lung carcinoma. Clin Cancer Res. 15:6820–6829. 2009. View Article : Google Scholar : PubMed/NCBI

42 

Liu ZC, Chen XH, Song HX, Wang HS, Zhang G, Wang H, Chen DY, Fang R, Liu H, Cai SH and Du J: Snail regulated by PKC/GSK-3β pathway is crucial for EGF-induced epithelial-mesenchymal transition (EMT) of cancer cells. Cell Tissue Res. 358:491–502. 2014. View Article : Google Scholar : PubMed/NCBI

43 

Gras B, Jacqueroud L, Wierinckx A, Lamblot C, Fauvet F, Lachuer J, Puisieux A and Ansieau S: Snail family members unequally trigger EMT and thereby differ in their ability to promote the neoplastic transformation of mammary epithelial cells. PLoS One. 9:e922542014. View Article : Google Scholar : PubMed/NCBI

44 

Wettstein G, Bellaye PS, Kolb M, Hammann A, Crestani B, Soler P, Marchal-Somme J, Hazoume A, Gauldie J, Gunther A, et al: Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation. FASEB J. 27:1549–1560. 2013. View Article : Google Scholar : PubMed/NCBI

45 

Zheng H and Kang Y: Multilayer control of the EMT master regulators. Oncogene. 33:1755–1763. 2014. View Article : Google Scholar : PubMed/NCBI

46 

Zhang J, Zhou Y and Yang Y: CCR7 pathway induces epithelial-mesenchymal transition through up-regulation of Snail signaling in gastric cancer. Med Oncol. 32:4672015.PubMed/NCBI

47 

Sullivan NJ, Sasser AK, Axel AE, Vesuna F, Raman V, Ramirez N, Oberyszyn TM and Hall BM: Interleukin-6 induces an epithelial-mesenchymal transition phenotype in human breast cancer cells. Oncogene. 28:2940–2947. 2009. View Article : Google Scholar : PubMed/NCBI

48 

Gonzalez-Moreno O, Lecanda J, Green JE, Segura V, Catena R, Serrano D and Calvo A: VEGF elicits epithelial-mesenchymal transition (EMT) in prostate intraepithelial neoplasia (PIN)-like cells via an autocrine loop. Exp Cell Res. 316:554–567. 2010. View Article : Google Scholar : PubMed/NCBI

49 

Mironchik Y, Winnard PT Jr, Vesuna F, Kato Y, Wildes F, Pathak AP, Kominsky S, Artemov D, Bhujwalla Z, van Diest P, et al: Twist overexpression induces in vivo angiogenesis and correlates with chromosomal instability in breast cancer. Cancer Res. 65:10801–10809. 2005. View Article : Google Scholar : PubMed/NCBI

50 

Wang Y, Yao X, Ge J, Hu F and Zhao Y: Can vascular endothelial growth factor and microvessel density be used as prognostic biomarkers for colorectal cancer? A systematic review and meta-analysis. ScientificWorldJournal. 2014:1027362014.PubMed/NCBI

51 

Maxwell PJ, Coulter J, Walker SM, McKechnie M, Neisen J, McCabe N, Kennedy RD, Salto-Tellez M, Albanese C and Waugh DJ: Potentiation of inflammatory CXCL8 signalling sustains cell survival in PTEN-deficient prostate carcinoma. Eur Urol. 64:177–88. 2013. View Article : Google Scholar : PubMed/NCBI

52 

Murphy C, McGurk M, Pettigrew J, Santinelli A, Mazzucchelli R, Johnston PG, Montironi R and Waugh DJ: Nonapical and cytoplasmic expression of interleukin-8, CXCR1, and CXCR2 correlates with cell proliferation and microvessel density in prostate cancer. Clin Cancer Res. 11:4117–4127. 2005. View Article : Google Scholar : PubMed/NCBI

53 

Ogura M, Takeuchi H, Kawakubo H, Nishi T, Fukuda K, Nakamura R, Takahashi T, Wada N, Saikawa Y, Omori T, et al: Clinical significance of CXCL-8/CXCR-2 network in esophageal squamous cell carcinoma. Surgery. 154:512–520. 2013. View Article : Google Scholar : PubMed/NCBI

54 

Uzunoglu FG, Yavari N, Bohn BA, Nentwich MF, Reeh M, Pantel K, Perez D, Tsui TY, Bockhorn M, Mann O, et al: C-X-C motif receptor 2, endostatin and proteinase-activated receptor 1 polymorphisms as prognostic factors in NSCLC. Lung Cancer. 81:123–129. 2013. View Article : Google Scholar : PubMed/NCBI

55 

Pecot CV, Rupaimoole R, Yang D, Akbani R, Ivan C, Lu C, Wu S, Han HD, Shah MY, Rodriguez-Aguayo C, et al: Tumour angiogenesis regulation by the miR-200 family. Nat Commun. 4:24272013. View Article : Google Scholar : PubMed/NCBI

56 

Mendonca MA, Souto FO, Micheli DC, Alves-Filho JC, Cunha FQ, Murta EF and Tavares-Murta BM: Mechanisms affecting neutrophil migration capacity in breast cancer patients before and after chemotherapy. Cancer Chemother Pharmacol. 73:317–324. 2014. View Article : Google Scholar : PubMed/NCBI

57 

Merritt WM, Lin YG, Spannuth WA, Fletcher MS, Kamat AA, Han LY, Landen CN, Jennings N, de Geest K, Langley RR, et al: Effect of interleukin-8 gene silencing with liposome-encapsulated small interfering RNA on ovarian cancer cell growth. J Natl Cancer Inst. 100:359–372. 2008. View Article : Google Scholar : PubMed/NCBI

58 

Papassava P, Gorgoulis VG, Papaevangeliou D, Vlahopoulos S, van Dam H and Zoumpourlis V: Overexpression of activating transcription factor-2 is required for tumor growth and progression in mouse skin tumors. Cancer Res. 64:8573–8584. 2004. View Article : Google Scholar : PubMed/NCBI

59 

Tindberg N, Porsmyr-Palmertz M and Simi A: Contribution of MAP kinase pathways to the activation of ATF-2 in human neuroblastoma cells. Neurochem Res. 25:527–531. 2000. View Article : Google Scholar : PubMed/NCBI

60 

Ricote M, Garcia-Tunon I, Bethencourt F, Fraile B, Onsurbe P, Paniagua R and Royuela M: The p38 transduction pathway in prostatic neoplasia. J Pathol. 208:401–407. 2006. View Article : Google Scholar : PubMed/NCBI

61 

Eliopoulos AG, Gallagher NJ, Blake SM, Dawson CW and Young LS: Activation of the p38 mitogen-activated protein kinase pathway by Epstein-Barr virus-encoded latent membrane protein 1 coregulates interleukin-6 and interleukin-8 production. J Biol Chem. 274:16085–16096. 1999. View Article : Google Scholar : PubMed/NCBI

62 

Wang L, Tang C, Cao H, Li K, Pang X, Zhong L, Dang W, Tang H, Huang Y, Wei L, et al: Activation of IL-8 via PI3K/Akt-dependent pathway is involved in leptin-mediated epithelial-mesenchymal transition in human breast cancer cells. Cancer Biol Ther. 16:1220–1230. 2015. View Article : Google Scholar : PubMed/NCBI

63 

Hill R, Calvopina JH, Kim C, Wang Y, Dawson DW, Donahue TR, Dry S and Wu H: PTEN loss accelerates KrasG12D-induced pancreatic cancer development. Cancer Res. 70:7114–7124. 2010. View Article : Google Scholar : PubMed/NCBI

64 

Yan W, Han P, Zhou Z, Tu W, Liao J, Li P, Liu M, Tian D and Fu Y: Netrin-1 induces epithelial-mesenchymal transition and promotes hepatocellular carcinoma invasiveness. Dig Dis Sci. 59:1213–1221. 2014. View Article : Google Scholar : PubMed/NCBI

65 

Song J, Feng L, Zhong R, Xia Z, Zhang L, Cui L, Yan H, Jia X and Zhang Z: Icariside II inhibits the EMT of NSCLC cells in inflammatory microenvironment via down-regulation of Akt/NF-κB signaling pathway. Mol Carcinog. 56:36–48. 2017. View Article : Google Scholar : PubMed/NCBI

66 

Voorzanger N, Touitou R, Garcia E, Delecluse HJ, Rousset F, Joab I, Favrot MC and Blay JY: Interleukin (IL)-10 and IL-6 are produced in vivo by non-Hodgkin's lymphoma cells and act as cooperative growth factors. Cancer Res. 56:5499–5505. 1996.PubMed/NCBI

67 

Carpenter RL, Paw I, Dewhirst MW and Lo HW: Akt phosphorylates and activates HSF-1 independent of heat shock, leading to Slug overexpression and epithelial-mesenchymal transition (EMT) of HER2-overexpressing breast cancer cells. Oncogene. 34:546–557. 2015. View Article : Google Scholar : PubMed/NCBI

68 

Baranwal S and Alahari SK: Molecular mechanisms controlling E-cadherin expression in breast cancer. Biochem Biophys Res Commun. 384:6–11. 2009. View Article : Google Scholar : PubMed/NCBI

69 

Moon HG, Zheng Y, An CH, Kim YK and Jin Y: CCN1 secretion induced by cigarette smoking extracts augments IL-8 release from bronchial epithelial cells. PLoS One. 8:e681992013. View Article : Google Scholar : PubMed/NCBI

70 

Cai J, Guan H, Fang L, Yang Y, Zhu X, Yuan J, Wu J and Li M: MicroRNA-374a activates Wnt/β-catenin signaling to promote breast cancer metastasis. J Clin Invest. 123:566–579. 2013.PubMed/NCBI

71 

Zappulli V, de Cecco S, Trez D, Caliari D, Aresu L and Castagnaro M: Immunohistochemical expression of E-cadherin and β-catenin in feline mammary tumours. J Comp Pathol. 147:161–170. 2012. View Article : Google Scholar : PubMed/NCBI

72 

Ahn SH, Park H, Ahn YH, Kim S, Cho MS, Kang JL and Choi YH: Necrotic cells influence migration and invasion of glioblastoma via NF-κB/AP-1-mediated IL-8 regulation. Sci Rep. 6:245522016. View Article : Google Scholar : PubMed/NCBI

73 

Cheng XS, Li YF, Tan J, Sun B, Xiao YC, Fang XB, Zhang XF, Li Q, Dong JH, Li M, et al: CCL20 and CXCL8 synergize to promote progression and poor survival outcome in patients with colorectal cancer by collaborative induction of the epithelial-mesenchymal transition. Cancer Lett. 348:77–87. 2014. View Article : Google Scholar : PubMed/NCBI

74 

Zhao ZW, Wang YX, Lv X, Nie YM and Wu J: Shear stress promotes epithelial-mesenchymal transition of laryngeal cancer cells by inducing IL-8/CXCR1-NF-Kappa B axis. J Invest Med. 62:S802014.

75 

Choi SH, Kwon OJ, Park JY, Kim DY, Ahn SH, Kim SU, Ro SW, Kim KS, Park JH, Kim S, et al: Inhibition of tumour angiogenesis and growth by small hairpin HIF-1α and IL-8 in hepatocellular carcinoma. Liver Int. 34:632–642. 2014. View Article : Google Scholar : PubMed/NCBI

76 

Wu S, Shang H, Cui L, Zhang Z, Zhang Y, Li Y, Wu J, Li RK and Xie J: Targeted blockade of interleukin-8 abrogates its promotion of cervical cancer growth and metastasis. Mol Cell Biochem. 375:69–79. 2013.PubMed/NCBI

77 

Pine SR, Mechanic LE, Enewold L, Chaturvedi AK, Katki HA, Zheng YL, Bowman ED, Engels EA, Caporaso NE and Harris CC: Increased levels of circulating interleukin 6, interleukin 8, C-reactive protein, and risk of lung cancer. J Natl Cancer Inst. 103:1112–1122. 2011. View Article : Google Scholar : PubMed/NCBI

78 

Xie K: Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev. 12:375–391. 2001. View Article : Google Scholar : PubMed/NCBI

79 

Bates RC, DeLeo MJ III and Mercurio AM: The epithelial-mesenchymal transition of colon carcinoma involves expression of IL-8 and CXCR-1-mediated chemotaxis. Exp Cell Res. 299:315–324. 2004. View Article : Google Scholar : PubMed/NCBI

80 

Yang JR, Pan TJ, Yang H, Wang T, Liu W, Liu B and Qian WH: Kindlin-2 promotes invasiveness of prostate cancer cells via NF-κB-dependent upregulation of matrix metalloproteinases. Gene. 576:571–576. 2016. View Article : Google Scholar : PubMed/NCBI

81 

Zucchini-Pascal N, Peyre L and Rahmani R: Crosstalk between beta-catenin and snail in the induction of epithelial to mesenchymal transition in hepatocarcinoma: Role of the ERK1/2 pathway. Int J Mol Sci. 14:20768–20792. 2013. View Article : Google Scholar : PubMed/NCBI

82 

Zhao J, Zhang ZR, Zhao N, Ma BA and Fan QY: VEGF silencing inhibits human osteosarcoma angiogenesis and promotes cell apoptosis via PI3K/AKT signaling pathway. Int J Clin Exp Med. 8:12411–12417. 2015.PubMed/NCBI

83 

Matsumoto G, Hirohata R, Hayashi K, Sugimoto Y, Kotani E, Shimabukuro J, Hirano T, Nakajima Y, Kawamata S and Mori H: Control of angiogenesis by VEGF and endostatin-encapsulated protein microcrystals and inhibition of tumor angiogenesis. Biomaterials. 35:1326–1333. 2014. View Article : Google Scholar : PubMed/NCBI

84 

Shen Y, Wang D and Wang X: Role of CCR2 and IL-8 in acute lung injury: A new mechanism and therapeutic target. Expert Rev Respir Med. 5:107–114. 2011. View Article : Google Scholar : PubMed/NCBI

85 

Skov L, Beurskens FJ, Zachariae CO, Reitamo S, Teeling J, Satijn D, Knudsen KM, Boot EP, Hudson D, Baadsgaard O, et al: IL-8 as antibody therapeutic target in inflammatory diseases: Reduction of clinical activity in palmoplantar pustulosis. J Immunol. 181:669–679. 2008. View Article : Google Scholar : PubMed/NCBI

86 

Hatfield KJ, Olsnes AM, Gjertsen BT and Bruserud Ø: Antiangiogenic therapy in acute myelogenous leukemia: Targeting of vascular endothelial growth factor and interleukin 8 as possible antileukemic strategies. Curr Cancer Drug Targets. 5:229–248. 2005. View Article : Google Scholar : PubMed/NCBI

87 

Li WH, Qiu Y, Zhang HQ, Liu Y, You JF, Tian XX and Fang WG: P2Y2 receptor promotes cell invasion and metastasis in prostate cancer cells. Br J Cancer. 109:1666–1675. 2013. View Article : Google Scholar : PubMed/NCBI

88 

Waugh DJ and Wilson C: The interleukin-8 pathway in cancer. Clin Cancer Res. 14:6735–6741. 2008. View Article : Google Scholar : PubMed/NCBI

89 

Schadendorf D, Möller A, Algermissen B, Worm M, Sticherling M and Czarnetzki BM: IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol. 151:2667–2675. 1993.PubMed/NCBI

90 

de Larco JE, Wuertz BR, Rosner KA, Erickson SA, Gamache DE, Manivel JC and Furcht LT: A potential role for interleukin-8 in the metastatic phenotype of breast carcinoma cells. Am J Pathol. 158:639–646. 2001. View Article : Google Scholar : PubMed/NCBI

91 

Maxwell PJ, Gallagher R, Seaton A, Wilson C, Scullin P, Pettigrew J, Stratford IJ, Williams KJ, Johnston PG and Waugh DJ: HIF-1 and NF-kappaB-mediated upregulation of CXCR1 and CXCR2 expression promotes cell survival in hypoxic prostate cancer cells. Oncogene. 26:7333–7345. 2007. View Article : Google Scholar : PubMed/NCBI

92 

Lattanzio L, Tonissi F, Torta I, Gianello L, Russi E, Milano G, Merlano M and Lo Nigro C: Role of IL-8 induced angiogenesis in uveal melanoma. Invest New Drugs. 31:1107–1114. 2013. View Article : Google Scholar : PubMed/NCBI

93 

Li KC, Huang YH, Ho CY, Chu CY, Cha ST, Tsai HH, Ko JY, Chang CC and Tan CT: The role of IL-8 in the SDF-1α/CXCR4-induced angiogenesis of laryngeal and hypopharyngeal squamous cell carcinoma. Oral Oncol. 48:507–515. 2012. View Article : Google Scholar : PubMed/NCBI

94 

Shen XH, Xu SJ, Jin CY, Ding F, Zhou YC and Fu GS: Interleukin-8 prevents oxidative stress-induced human endothelial cell senescence via telomerase activation. Int Immunopharmacol. 16:261–267. 2013. View Article : Google Scholar : PubMed/NCBI

95 

Rofstad EK and Halsør EF: Vascular endothelial growth factor, interleukin 8, platelet-derived endothelial cell growth factor, and basic fibroblast growth factor promote angiogenesis and metastasis in human melanoma xenografts. Cancer Res. 60:4932–4938. 2000.PubMed/NCBI

96 

Shahzad MM, Arevalo JM, Armaiz-Pena GN, Lu C, Stone RL, Moreno-Smith M, Nishimura M, Lee JW, Jennings NB, Bottsford-Miller J, et al: Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and metastasis. J Biol Chem. 285:35462–3547070. 2010. View Article : Google Scholar : PubMed/NCBI

97 

Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, Wicinski J, Cabaud O, Charafe-Jauffret E, Birnbaum D, et al: CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts. J Clin Invest. 120:485–497. 2010. View Article : Google Scholar : PubMed/NCBI

98 

Sparmann A and Bar-Sagi D: Ras-induced interleukin-8 expression plays a critical role in tumor growth and angiogenesis. Cancer Cell. 6:447–458. 2004. View Article : Google Scholar : PubMed/NCBI

99 

Yin J, Zeng F, Wu N, Kang K, Yang Z and Yang H: Interleukin-8 promotes human ovarian cancer cell migration by epithelial-mesenchymal transition induction in vitro. Clin Transl Oncol. 17:365–370. 2015. View Article : Google Scholar : PubMed/NCBI

100 

Kim SW, Hayashi M, Lo JF, Fearns C, Xiang R, Lazennec G, Yang Y and Lee JD: Tid1 negatively regulates the migratory potential of cancer cells by inhibiting the production of interleukin-8. Cancer Res. 65:8784–8791. 2005. View Article : Google Scholar : PubMed/NCBI

101 

Luca M, Huang S, Gershenwald JE, Singh RK, Reich R and Bar-Eli M: Expression of interleukin-8 by human melanoma cells up-regulates MMP-2 activity and increases tumor growth and metastasis. Am J Pathol. 151:1105–1113. 1997.PubMed/NCBI

102 

Sheridan C, Kishimoto H, Fuchs RK, Mehrotra S, Bhat-Nakshatri P, Turner CH, Badve R Jr, Goulet S and Nakshatri H: CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: An early step necessary for metastasis. Breast Cancer Res. 8:R592006. View Article : Google Scholar : PubMed/NCBI

103 

Haro A, Yano T, Kohno M, Yoshida T, Koga T, Okamoto T, Takenoyama M and Maehara Y: Expression of Brachyury gene is a significant prognostic factor for primary lung carcinoma. Ann Surg Oncol. 20 Suppl 3:S509–S516. 2013. View Article : Google Scholar : PubMed/NCBI

104 

Choi J, Song N, Han S, Chung S, Sung H, Lee JY, Jung S, Park SK, Yoo KY, Han W, et al: The associations between immunity-related genes and breast cancer prognosis in Korean women. PLoS One. 9:e1035932014. View Article : Google Scholar : PubMed/NCBI

105 

Hanker LC, Rody A, Holtrich U, Pusztai L, Ruckhaeberle E, Liedtke C, Ahr A, Heinrich TM, Sänger N, Becker S and Karn T: Prognostic evaluation of the B cell/IL-8 metagene in different intrinsic breast cancer subtypes. Breast Cancer Res Treat. 137:407–16. 2013. View Article : Google Scholar : PubMed/NCBI

106 

Reitter EM, Ay C, Kaider A, Pirker R, Zielinski C, Zlabinger G and Pabinger I: Interleukin levels and their potential association with venous thromboembolism and survival in cancer patients. Clin Exp Immunol. 177:253–260. 2014. View Article : Google Scholar : PubMed/NCBI

107 

Wang S, Wu X, Zhang J, Chen Y, Xu J, Xia X, He S, Qiang F, Li A, Shu Y, et al: CHIP functions as a novel suppressor of tumour angiogenesis with prognostic significance in human gastric cancer. Gut. 62:496–508. 2013. View Article : Google Scholar : PubMed/NCBI

108 

Manna S, Singha B, Phyo SA, Gatla HR, Chang TP, Sanacora S, Ramaswami S and Vancurova I: Proteasome inhibition by bortezomib increases IL-8 expression in androgen-independent prostate cancer cells: The role of IKKα. J Immunol. 191:2837–2846. 2013. View Article : Google Scholar : PubMed/NCBI

109 

Han J, Bae SY, Oh SJ, Lee J, Lee JH, Lee HC, Lee SK, Kil WH, Kim SW, Nam SJ, et al: Zerumbone suppresses IL-1β-induced cell migration and invasion by inhibiting IL-8 and MMP-3 expression in human triple-negative breast cancer cells. Phytother Res. 28:1654–1660. 2014. View Article : Google Scholar : PubMed/NCBI

110 

Epanchintsev A, Shyamsunder P, Verma RS and Lyakhovich A: IL-6, IL-8, MMP-2, MMP-9 are overexpressed in Fanconi anemia cells through a NF-κB/TNF-α dependent mechanism. Mol Carcinog. 54:1686–1699. 2015. View Article : Google Scholar : PubMed/NCBI

111 

Dong P, Xiong Y, Watari H, Hanley SJ, Konno Y, Ihira K, Yamada T, Kudo M, Yue J and Sakuragi N: MiR-137 and miR-34a directly target Snail and inhibit EMT, invasion and sphere-forming ability of ovarian cancer cells. J Exp Clin Cancer Res. 35:1322016. View Article : Google Scholar : PubMed/NCBI

112 

Meng J, Zhang XT, Liu XL, Fan L, Li C, Sun Y, Liang XH, Wang JB, Mei QB, Zhang F and Zhang T: WSTF promotes proliferation and invasion of lung cancer cells by inducing EMT via PI3K/Akt and IL-6/STAT3 signaling pathways. Cell Signal. 28:1673–1682. 2016. View Article : Google Scholar : PubMed/NCBI

113 

Huang T, Chen Z and Fang L: Curcumin inhibits LPS-induced EMT through downregulation of NF-κB-snail signaling in breast cancer cells. Oncol Rep. 29:117–124. 2013.PubMed/NCBI

114 

Zhang Z, Chen H, Xu C, Song L, Huang L, Lai Y, Wang Y, Chen H, Gu D, Ren L and Yao Q: Curcumin inhibits tumor epithelial-mesenchymal transition by downregulating the Wnt signaling pathway and upregulating NKD2 expression in colon cancer cells. Oncol Rep. 35:2615–2623. 2016.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhao Z, Wang S, Lin Y, Miao Y, Zeng Y, Nie Y, Guo P, Jiang G and Wu J: Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review). Oncol Lett 13: 4577-4584, 2017.
APA
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y. ... Wu, J. (2017). Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review). Oncology Letters, 13, 4577-4584. https://doi.org/10.3892/ol.2017.6034
MLA
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y., Guo, P., Jiang, G., Wu, J."Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review)". Oncology Letters 13.6 (2017): 4577-4584.
Chicago
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y., Guo, P., Jiang, G., Wu, J."Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review)". Oncology Letters 13, no. 6 (2017): 4577-4584. https://doi.org/10.3892/ol.2017.6034
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao Z, Wang S, Lin Y, Miao Y, Zeng Y, Nie Y, Guo P, Jiang G and Wu J: Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review). Oncol Lett 13: 4577-4584, 2017.
APA
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y. ... Wu, J. (2017). Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review). Oncology Letters, 13, 4577-4584. https://doi.org/10.3892/ol.2017.6034
MLA
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y., Guo, P., Jiang, G., Wu, J."Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review)". Oncology Letters 13.6 (2017): 4577-4584.
Chicago
Zhao, Z., Wang, S., Lin, Y., Miao, Y., Zeng, Y., Nie, Y., Guo, P., Jiang, G., Wu, J."Epithelial-mesenchymal transition in cancer: Role of the IL-8/IL-8R axis (Review)". Oncology Letters 13, no. 6 (2017): 4577-4584. https://doi.org/10.3892/ol.2017.6034
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team