Abstract
Current evidence indicates that the abnormal expression of chemokines or their receptors, such as CXC chemokine receptor-4 (CXCR4), is positively correlated with the development, progression and metastasis of tumor cells. However, the role of CXCR4 in neuroblastoma and its response to chemotherapy remain largely unclear. In addition, forkhead box 3 (Foxp3), a transcription factor associated with T cell tolerance, is expressed in tumor cells and plays a role in the immune evasion of cancers. The present study aimed to examine the expression of CXCR4 and Foxp3 in the LAN-5 and SK-N-SH neuroblastoma cell lines. The effects of chemotherapy drugs, cyclophosphamide (CTX) and pirarubicin (THP), on the expression of these two genes were also investigated. Our findings indicated that CXCR4 and Foxp3 were highly expressed in LAN-5 and SK-N-SH cells. Following treatment with CTX and THP, the protein expression of CXCR4 in LAN-5 and SK-N-SH cells was significantly decreased (P<0.05). The expression of Foxp3 in LAN-5 cells was also significantly downregulated by CTX and THP treatment (P<0.05). Therefore, the high expression of CXCR4 and Foxp3 in LAN-5 and SK-N-SH cells and their subsequent downregulation following administration of the chemotherapy agents suggests that the chemokine receptors, CXCR4 and Foxp3, may be involved in the metastasis and tumor evasion of neuroblastoma. Further studies should investigate the expression of CXCR4 and Foxp3 in patient samples.
Highlights
Proinflammatory cytokines, including chemokines, attack inflammatory cells and regulate hematopoietic cell migration to bone marrow or lymph nodes and neuronal migration [1,2]
The LAN‐5 neuroblastoma cell line was kindly provided by Dr Stuart Elliott Siegel (Children's Hospital Los Angeles, Los Angeles, CA, USA) and the origin has been described previously [17,18]; the SK‐N‐SH cell line was purchased from American Type Culture Collection (Cambridge, MA, USA)
To investigate the role of CXC chemokine receptor‐4 (CXCR4) in the progression and metastasis of neuroblastoma, the expression of CXCR4 in LAN‐5 and SK‐N‐SH cells was analyzed by FACS
Summary
Proinflammatory cytokines, including chemokines, attack inflammatory cells and regulate hematopoietic cell migration to bone marrow or lymph nodes and neuronal migration [1,2]. Abnormal expression of chemokines or Neuroblastoma is one of the most common types of solid tumor found in children worldwide. As metastasis of neuroblastoma occurs at a high frequency [12], metastasis is the ultimate step in the progression of tumor cells toward autonomy from the host, it is required to identify the mechanisms underlying tumor cell metastasis. The abnormal expression of CXCR4 and Foxp may be involved in the metastasis and immune evasion of other types of tumors [13,14,15,16], their role in neuroblastoma and their response to chemotherapy remain largely unclear. The present study aimed to examine the expression of CXCR4 and Foxp in neuroblastoma cell lines LAN‐5 and SK‐N‐SH. The effects of chemotherapy drugs, such as cyclophosphamide (CTX) and pirarubicin (THP), on the expression of CXCR4 and Foxp were investigated
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