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TNF-α augments CXCR2 and CXCR3 to promote progression of renal cell carcinoma
<span title="2016-06-14">2016</span>
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<a target="_blank" rel="noopener" href="https://fatcat.wiki/container/o6okgawz35b2tfswpfwce3dreq" style="color: black;">Journal of Cellular and Molecular Medicine</a>
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Within the tumour microenvironment, a complex network of chemokines and their receptors affects the initiation and progression of tumours. The higher levels of tumour necrosis factor-alpha (TNF-a) are associated with tumour progression and an anti-TNF-a monoclonal antibody has been used successfully to treat patients with renal cell carcinoma (RCC). However, the role of chemokines and their receptors in the TNF-a-promoted progression of RCC remains unclear. In this study, TNF-a was found to
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<a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1111/jcmm.12890">doi:10.1111/jcmm.12890</a>
<a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pubmed/27297979">pmid:27297979</a>
<a target="_blank" rel="external noopener" href="https://pubmed.ncbi.nlm.nih.gov/PMC5082409/">pmcid:PMC5082409</a>
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... nce the migration, invasion and epithelial-mesenchymal transition (EMT) of RCC cells. To further investigate the molecular mechanism of TNF-a on the progression of RCC, reverse transcription and quantitative PCR was used to screen chemokines and chemokine receptors that were associated with tumorigenesis. The results showed that TNF-a significantly increased the expressions of CXCR2 and CXCR3 and their related ligands in RCC cells. Subsequently, we used a lentiviral shRNA system to knockdown the expression of CXCR2 and/or CXCR3 in RCC cells. CXCR2 and CXCR3 silencing inhibited the induction of Slug and ZEB-1 with TNF-a treatment of RCC cells. In addition, the knockdown of both CXCR2 and CXCR3 resulted in a greater decrease in cell migration, invasion and clonogenic ability compared with either CXCR2 or CXCR3 knockdown alone. Moreover, CXCR2 and CXCR3 silencing significantly reduced the sphere-forming ability of RCC cells. High expression levels of CXCR2 and CXCR3 in cancer tissues correlated with tumour progression of renal cell carcinoma. These findings suggest that TNF-a augments CXCR2 and CXCR3 to promote the progression of renal cell carcinoma leading to a poor prognosis.
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