The expression of functional chemokine receptor CXCR4 is associated with the metastatic potential of human nasopharyngeal carcinoma.
OBJECTIVE
Chemokine receptors are implicated in metastasis of several malignant tumors. This study was done to evaluate the contribution of chemokine receptors CXCR4 and CCR7 to metastasis of human nasopharyngeal carcinoma.


METHODS
Reverse transcription-PCR, immunohistochemistry, and flow cytometry were used to evaluate mRNA and protein expression of CXCR4 and CCR7 in nasopharyngeal carcinoma tumor tissues and cell lines. Chemotaxis assays were used to evaluate the function of CXCR4 in nasopharyngeal carcinoma cells. Antisense CXCR4 was used to inhibit receptor expression and to block metastasis of human nasopharyngeal carcinoma cells in vivo in athymic mice.


RESULTS
CXCR4 protein was detected in tumor cells in 31 of 40 primary human nasopharyngeal carcinoma and in 13 of 15 lymph node metastases. CXCR4 transcripts were detected in eight CXCR4 protein-positive primary nasopharyngeal carcinoma tissues and seven nasopharyngeal carcinoma cell lines tested. On the other hand, the transcripts for CCR7 were detected only in four primary nasopharyngeal carcinoma tissues and in none of the nasopharyngeal carcinoma cell lines. In functional experiments, metastatic nasopharyngeal carcinoma cell lines that expressed high levels of CXCR4 were found to migrate in response to the CXCR4 ligand SDF-1alpha. Transfection of antisense CXCR4 in metastatic nasopharyngeal carcinoma cells inhibited the expression of CXCR4 and SDF-1alpha-induced cell migration in vitro and reduced the capacity of the tumor cells to form metastasis in the lungs and lymph nodes when injected in athymic mice.


CONCLUSIONS
The expression of functional CXCR4 but not CCR7 is correlated with the metastatic potential of human nasopharyngeal carcinoma cells. Therefore, CXCR4 may be considered as a potential target for the prevention of nasopharyngeal carcinoma metastasis.
Cancer Research Institute, Xiang-Ya School of Medicine, Central South University, Hunan, PR China.
Jinyue
J
Hu
Xiyun
X
Deng
Xiuwu
X
Bian
Guancheng
G
Li
Yongqing
Y
Tong
Yuehui
Y
Li
Qingliang
Q
Wang
Rong
R
Xin
Xiaojuan
X
He
Guohua
G
Zhou
Pingli
P
Xie
Yanwen
Y
Li
Ji Ming
JM
Wang
Ya
Y
Cao
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D016373:DNA, Antisense / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009303:Nasopharyngeal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023041:Xenograft Model Antitumor Assays / Q000379:methods
C515370:CCR7 protein, human; C515371:Ccr7 protein, mouse; D016373:DNA, Antisense; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine