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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Brain Neoplasms, Cell Line, Tumor, Cell Movement, Chemokine CXCL12, Coculture Techniques, Humans, Macrophages, NF-kappa B, Neoplasm Invasiveness, Neuroblastoma, Receptors, CXCR4, Signal Transduction, Up-Regulation.
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Does nF-κB signaling pathway confer neuroblastoma cells migration and invasion ability via the regulation of CXCR4? Context: Accumulating evidence implicates the transcription factor NF-κB as a positive mediator of tumor metastasis, but the molecular mechanism(s) involved in this process remains largely unknown. In this study, we investigated the role of NF-κB signaling pathway in the regulation of CXC chemokine receptor-4 (CXCR4) in neuroblastoma metastasis. NF-κB, CXCR4 mRNA and protein expression were measured by RT-PCR, and Western blot. Tumor necrosis factor-α (TNF-α) was used to induce the upregulation of NF-κB and CXCR4. The knockdown of NF-κB and CXCR4 was achieved by PDTC. Transwell assay was used to investigate the role of NF-κB (P65) in neuroblastoma cell migration and invasion. An in vitro co-culture system was established to investigate the role of tumor microenvironment in regulation of the NF-κB signaling pathway. Over-expression of NF-κB (p65) promoted tumor migration and invasion through the upregulation of CXCR4; however, knockdown of NF-κB(P65) inhibited tumor migration and invasion through blocking the expression of CXCR4. Consistently, in the co-culture system, the expression of CXCR4 was partly dependent on the expression of NF-κB (p65).
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Our studies reveal critical roles for the NF-κB signaling pathway in neuroblastoma migration and invasion. The mechanism may be through up-regulation of CXCR4, mediated by the NF-κB signaling pathways. Targeting NF-κB signalling pathways and ultimately CXCR4 could be a strategy in neuroblastoma therapy. Final Decision: yes