The Expression of Functional Chemokine Receptor CXCR4 Is Associated with the Metastatic Potential of Human Nasopharyngeal Carcinoma

Abstract

Purpose: 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. Experimental Design: 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 31of 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-1a. Transfection of antisense CXCR4 in metastatic nasopharyngeal carcinoma cells inhibited the expression of CXCR4 and SDF-1a-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. Conclusion: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.

Expression and potential role of chemokine receptor CXCR4 in human bladder carcinoma cell lines with different metastatic ability

“…The chemokine receptor cXcr4 has been considered one of the mechanisms related to bladder tumor cell metastasis. Tumors that express higher levels of cXcr4 have been found to be more prone to cancer metastasis than those with lower expression (12,13). it is well known that peripheral lymphocytes preferentially localize to peripheral lymphoid tissues, such as the lymph nodes; this is called the homing phenomenon (14).…”

Roles of Chemokine Receptor 4 (CXCR4) and Chemokine Ligand 12 (CXCL12) in Metastasis of Hepatocellular Carcinoma Cells

“…Many studies suggest that tumor cell migration and organspecific metastasis are critically regulated by chemokines and their receptors (21)(22)(23)(24)(25)(26)(27)(28)(29). The axis of CXCR4/CXCL12 plays an important role in metastasis of many tumors (9)(10)(11)(12)(13)(14)(22)(23)(24)(25).…”

“…Chemotaxis assays were done using 48-well chemotaxis chambers (Neuro Probe, Cabin John, MD) as described previously (21). Aliquots of 27 to 29-μl assay medium (RPMI 1640 containing 1% bovine serum albumin, 30 mmol/L HEPES) containing different concentrations of CXCL12 were placed in the lower wells of the chamber.…”

Chemokines in tumor angiogenesis and metastasis

“…Patients with high CXCR4 expression in NSCLC, colorectal or prostate cancer were more prone to metastasis [149][150][151]. The expression of CXCR4 in nasopharyngeal carcinoma and osteosarcoma is also associated with metastasis [152,153]. In colorectal cancer, CXCR4 expression in primary tumors demonstrated significant association with recurrence, survival, and liver metastasis [154].…”