The independent, unfavorable prognostic factors endothelin A receptor and chemokine receptor 4 have a close relationship in promoting the motility of nasopharyngeal carcinoma cells via the activation of AKT and MAPK pathways

Journal of Translational Medicine

Hai-Qiang Mai²  Xiang Guo²  Pei-Yu Huang²  Hao-Yuan Mo²  Lin-Quan Tang²  Lu Zhang²  Hui-Zhong Zhang³  Li-Hua Xu¹  Huai Liu²  Qiu-Yan Chen²  Dong-Hua Luo² 

[1] Center of Oncology and Hematology, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou P. R. China;Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong 510060, P. R. China;Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong 510060, P. R. China

关键词: Metastasis;    CXCR4;    ETAR;    Prognosis;    Nasopharyngeal carcinoma;   

Others  :  826732
DOI  :  10.1186/1479-5876-11-203

 received in 2012-12-26, accepted in 2013-08-23,  发布年份 2013

【 摘 要 】

Background

Recent studies have indicated that the expression of endothelin A receptor (ETAR) and chemokine receptor 4 (CXCR4) could be used as an indicator of the metastatic potential of nasopharyngeal carcinoma (NPC). The aim of this study was to determine the prognostic value of ETAR and CXCR4 in NPC patients and to reveal the interplay of the endothelin-1 (ET-1)/ETAR and stromal-derived factor-1(SDF-1)/CXCR4 pathways in promoting NPC cell motility.

Methods

Survival analysis was used to analyze the prognostic value of ETAR and CXCR4 expression in 153 cases of NPC. Chemotaxis assays were used to evaluate alterations in the migration ability of non-metastatic 6-10B and metastatic 5-8F NPC cells. Real-time PCR, immunoblotting, and flow cytometric analyses were used to evaluate changes in the expression levels of CXCR4 mRNA and protein induced by ET-1.

Results

The expression levels of ETAR and CXCR4 were closely related to each other and both correlated with a poor prognosis. A multivariate analysis showed that the expression levels of both ETAR and CXCR4 were independent prognostic factors for overall survival (OS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). The migration of 6-10B and 5-8F cells was elevated by ET-1 in combination with SDF-1α. The knockdown of ETAR protein expression by siRNA reduced CXCR4 protein expression in addition to ETAR protein expression, leading to a decrease in the metastatic potential of the 5-8F cells. ET-1 induced CXCR4 mRNA and protein expression in the 6-10B NPC cells in a time- and concentration-dependent fashion and was inhibited by an ETAR antagonist and PI3K/AKT/mTOR and MAPK/ERK1/2 pathway inhibitors.

Conclusions

ETAR and CXCR4 expression levels are potential prognostic biomarkers in NPC patients. ETAR activation partially promoted NPC cell migration via a mechanism that enhanced functional CXCR4 expression.

【 授权许可】

   
2013 Luo et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 1.

Figure 4.

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