TNF-α augments CXCR2 and CXCR3 to promote progression of renal cell carcinoma

Kuang-Hui Sun, Guang-Huan Sun, Yi-Ching Wu, Bai-Jiun Ko, Hui-Tzu Hsu, Sheng-Tang Wu
<span title="2016-06-14">2016</span> <i title="Wiley"> <a target="_blank" rel="noopener" href="" style="color: black;">Journal of Cellular and Molecular Medicine</a> </i> &nbsp;
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
more &raquo; ... 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.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1111/jcmm.12890</a> <a target="_blank" rel="external noopener" href="">pmid:27297979</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC5082409</a> <a target="_blank" rel="external noopener" href="">fatcat:sgfszkwfq5g7beuzxu4umn5b2i</a> </span>
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