Skip to main content
SpringerLink
Log in

Overexpression of CCL20 and its receptor CCR6 predicts poor clinical prognosis in human gliomas

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Recent studies have demonstrated that the chemokine CCL20 and its receptor CCR6 may be involved in tumorigenesis, tumor progression and metastatic spread of various human malignancies. The aim of this study was to investigate the clinicopathological significance and prognostic value of CCL20 and CCR6 expression in human malignant glioma. CCL20 and CCR6 expression in human gliomas and nonneoplastic brain tissues was measured by immunohistochemistry. The association of CCL20 and CCR6 expression with clinicopathological factors or prognosis in glioma patients was statistically analyzed. The expression levels of CCL20 and CCR6 proteins were both up-regulated in glioma tissues. There was a significantly positive correlation between the expression of the two markers (r = 0.88; P < 0.001). In addition, the overexpressions of CCL20 and CCR6 were both detected in high-grade glioma tissues compared with those in low-grade tissues and increased with ascending tumor World Health Organization (WHO) grades (P = 0.006 and 0.008, respectively). The increased expressions of CCL20 and CCR6 proteins were also significantly correlated with low Karnofsky performance score (both P = 0.01). Moreover, univariate analysis found that CCL20 expression (P = 0.002), CCR6 expression (P = 0.002) and CCL20/CCR6 co-expression (P < 0.001) were all significantly associated with poor prognosis. In particular, glioma patients with CCL20/CCR6 co-expression have the shortest overall survival. Multivariate analysis further identified the expression levels of CCL20 and CCR6 to be independent prognostic factors. Our data suggest for the first time that CCL20 and CCR6 might play an important role in the regulation of aggressiveness in human gliomas. The up-regulation of CCL20 and CCR6 might be closely associated with poor clinical outcome of patients with gliomas.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Zhang X, Yang H, Gong B, Jiang C, Yang L. Combined gene expression and protein interaction analysis of dynamic modularity in glioma prognosis. J Neurooncol. 2012;107:281–8.

    Article  PubMed  CAS  Google Scholar 

  2. Chu SH, Ma YB, Feng DF, et al. Correlation of low SLC22A18 expression with poor prognosis in patients with glioma. J Clin Neurosci. 2012;19:95–8.

    Article  PubMed  CAS  Google Scholar 

  3. Curran WJ Jr, Scott CB. Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys. 1996;36:1279–80.

    Article  PubMed  Google Scholar 

  4. Yoshie O, Imai T, Nomiyama H. Chemokines in immunity. Adv Immunol. 2001;78:57–110.

    Article  PubMed  CAS  Google Scholar 

  5. Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000;52:145–76.

    PubMed  CAS  Google Scholar 

  6. Rubie C, Frick VO, Wagner M, et al. Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases. World J Gastroenterol. 2006;12:6627–33.

    PubMed  CAS  Google Scholar 

  7. Wolff HA, Rolke D, Rave-Fränk M, et al. Analysis of chemokine and chemokine receptor expression in squamous cell carcinoma of the head and neck (SCCHN) cell lines. Radiat Environ Biophys. 2011;50:145–54.

    Article  PubMed  CAS  Google Scholar 

  8. Zhu B, Zou L, Cheng X, et al. Administration of MIP-3alpha gene to the tumor following radiation therapy boosts anti-tumor immunity in a murine model of lung carcinoma. Immunol Lett. 2006;103:101–7.

    Article  PubMed  CAS  Google Scholar 

  9. Yao T, Lin Z. MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta. 2012;1822:248–60.

    Article  PubMed  CAS  Google Scholar 

  10. Chang KP, Kao HK, Yen TC, et al. Overexpression of macrophage inflammatory protein-3α in oral cavity squamous cell carcinoma is associated with nodal metastasis. Oral Oncol. 2011;47:108–13.

    Article  PubMed  CAS  Google Scholar 

  11. Ding X, Wang K, Wang H, et al. High expression of CCL20 is associated with poor prognosis in patients with hepatocellular carcinoma after curative resection. J Gastrointest Surg. 2012;16:828–36.

    Article  PubMed  Google Scholar 

  12. Chang KP, Hao SP, Chang JH, et al. Macrophage inflammatory protein-3alpha is a novel serum marker for nasopharyngeal carcinoma detection and prediction of treatment outcomes. Clin Cancer Res. 2008;14:6979–87.

    Article  PubMed  CAS  Google Scholar 

  13. Uchida H, Iwashita Y, Sasaki A, et al. Chemokine receptor CCR6 as a prognostic factor after hepatic resection for hepatocellular carcinoma. J Gastroenterol Hepatol. 2006;21:161–8.

    Article  PubMed  CAS  Google Scholar 

  14. Ohtani H, Nakayama T, Yoshie O. In situ expression of the CCL20-CCR6 axis in lymphocyte-rich gastric cancer and its potential role in the formation of lymphoid stroma. Pathol Int. 2011;61:645–51.

    Article  PubMed  CAS  Google Scholar 

  15. Kimsey TF, Campbell AS, Albo D, Wilson M, Wang TN. Co-localization of macrophage inflammatory protein-3alpha (Mip-3alpha) and its receptor, CCR6, promotes pancreatic cancer cell invasion. Cancer J. 2004;10:374–80.

    Article  PubMed  CAS  Google Scholar 

  16. Giuliani N, Lisignoli G, Colla S, et al. CC-chemokine ligand 20/macrophage inflammatory protein-3α and CC-chemokine receptor 6 are overexpressed in myeloma microenvironment related to osteolytic bone lesions. Cancer Res. 2008;68:6840–50.

    Article  PubMed  CAS  Google Scholar 

  17. Sutherland A, Mirjolet JF, Maho A, Parmentier M. Expression of the chemokine receptor CCR6 in the Lewis lung carcinoma (LLC) cell line reduces its metastatic potential in vivo. Cancer Gene Ther. 2007;14:847–57.

    Article  PubMed  CAS  Google Scholar 

  18. Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.

    Article  PubMed  Google Scholar 

  19. Rubie C, Frick VO, Ghadjar P, et al. CCL20/CCR6 expression profile in pancreatic cancer. J Transl Med. 2010;8:45.

    Article  PubMed  Google Scholar 

  20. Ghadjar P, Loddenkemper C, Coupland SE, et al. Chemokine receptor CCR6 expression level and aggressiveness of prostate cancer. J Cancer Res Clin Oncol. 2008;134:1181–9.

    Article  PubMed  CAS  Google Scholar 

  21. Cassier PA, Treilleux I, Bachelot T, et al. Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer. BMC Cancer. 2011;11:213.

    Article  PubMed  CAS  Google Scholar 

  22. Liu J, Zhang N, Li Q, et al. Tumor-associated macrophages recruit CCR6+ regulatory T cells and promote the development of colorectal cancer via enhancing CCL20 production in mice. PLoS One. 2011;6:e19495.

    Article  PubMed  CAS  Google Scholar 

  23. Fushimi T, Kojima A, Moore MA, Crystal RG. Macrophage inflammatory protein 3alpha transgene attracts dendritic cells to established murine tumors and suppresses tumor growth. J Clin Invest. 2000;105:1383–93.

    Article  PubMed  CAS  Google Scholar 

  24. Bonnotte B, Crittenden M, Larmonier N, Gough M, Vile RG. MIP-3alpha transfection into a rodent tumor cell line increases intratumoral dendritic cell infiltration but enhances (facilitates) tumor growth and decreases immunogenicity. J Immunol. 2004;173:4929–35.

    PubMed  CAS  Google Scholar 

  25. Rubie C, Frick VO, Ghadjar P, et al. Effect of preoperative FOLFOX chemotherapy on CCL20/CCR6 expression in colorectal liver metastases. World J Gastroenterol. 2011;17:3109–16.

    PubMed  Google Scholar 

  26. Kirshberg S, Izhar U, Amir G, et al. Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression. PLoS One. 2011;6:e24856.

    Article  PubMed  CAS  Google Scholar 

  27. Chen KJ, Lin SZ, Zhou L, et al. Selective recruitment of regulatory T cell through CCR6-CCL20 in hepatocellular carcinoma fosters tumor progression and predicts poor prognosis. PLoS One. 2011;6:e24671.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Neurosurgery, Tangdu Hospital, No. 569, Xinsi Road, Baqiao District, Xi’an City, 710038, China

    Liang Wang, Huaizhou Qin, Lihong Li, Fuqiang Feng, Peigang Ji, Jingyu Zhang, Gang Li, Zhenwei Zhao & Guodong Gao

  2. Department of Experimental Surgery, Tangdu Hospital, No. 569, Xinsi Road, Baqiao District, Xi’an City, 710038, China

    Yongsheng Zhang & Yanyang TU

Authors
  1. Liang Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Huaizhou Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lihong Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yongsheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanyang TU
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fuqiang Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Peigang Ji
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jingyu Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Zhenwei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Guodong Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Zhenwei Zhao or Guodong Gao.

Additional information

Liang Wang, Huaizhou Qin and Lihong Li offer the equal contributions to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, L., Qin, H., Li, L. et al. Overexpression of CCL20 and its receptor CCR6 predicts poor clinical prognosis in human gliomas. Med Oncol 29, 3491–3497 (2012). https://doi.org/10.1007/s12032-012-0314-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-012-0314-9

Keywords

Search

Navigation