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Published in: Medical Oncology 5/2012

01-12-2012 | Original Paper

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

Authors: Liang Wang, Huaizhou Qin, Lihong Li, Yongsheng Zhang, Yanyang TU, Fuqiang Feng, Peigang Ji, Jingyu Zhang, Gang Li, Zhenwei Zhao, Guodong Gao

Published in: Medical Oncology | Issue 5/2012

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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.
Literature
1.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
2.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
3.
go back to reference Curran WJ Jr, Scott CB. Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys. 1996;36:1279–80.PubMedCrossRef Curran WJ Jr, Scott CB. Radiosurgery for glioma patients: hope or hype? Int J Radiat Oncol Biol Phys. 1996;36:1279–80.PubMedCrossRef
5.
go back to reference Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000;52:145–76.PubMed Murphy PM, Baggiolini M, Charo IF, et al. International union of pharmacology. XXII. Nomenclature for chemokine receptors. Pharmacol Rev. 2000;52:145–76.PubMed
6.
go back to reference 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 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
7.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
8.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
9.
go back to reference Yao T, Lin Z. MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta. 2012;1822:248–60.PubMedCrossRef Yao T, Lin Z. MiR-21 is involved in cervical squamous cell tumorigenesis and regulates CCL20. Biochim Biophys Acta. 2012;1822:248–60.PubMedCrossRef
10.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
11.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
12.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
13.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
17.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.PubMedCrossRef Dunbar E, Yachnis AT. Glioma diagnosis: immunohistochemistry and beyond. Adv Anat Pathol. 2010;17:187–201.PubMedCrossRef
19.
go back to reference Rubie C, Frick VO, Ghadjar P, et al. CCL20/CCR6 expression profile in pancreatic cancer. J Transl Med. 2010;8:45.PubMedCrossRef Rubie C, Frick VO, Ghadjar P, et al. CCL20/CCR6 expression profile in pancreatic cancer. J Transl Med. 2010;8:45.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
22.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
24.
go back to reference 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 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
25.
go back to reference 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 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
26.
go back to reference Kirshberg S, Izhar U, Amir G, et al. Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression. PLoS One. 2011;6:e24856.PubMedCrossRef Kirshberg S, Izhar U, Amir G, et al. Involvement of CCR6/CCL20/IL-17 axis in NSCLC disease progression. PLoS One. 2011;6:e24856.PubMedCrossRef
27.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
Metadata
Title
Overexpression of CCL20 and its receptor CCR6 predicts poor clinical prognosis in human gliomas
Authors
Liang Wang
Huaizhou Qin
Lihong Li
Yongsheng Zhang
Yanyang TU
Fuqiang Feng
Peigang Ji
Jingyu Zhang
Gang Li
Zhenwei Zhao
Guodong Gao
Publication date
01-12-2012
Publisher
Springer US
Published in
Medical Oncology / Issue 5/2012
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-012-0314-9

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