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="https://fatcat.wiki/container/o6okgawz35b2tfswpfwce3dreq" 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="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> <a target="_blank" rel="external noopener" href="https://fatcat.wiki/release/sgfszkwfq5g7beuzxu4umn5b2i">fatcat:sgfszkwfq5g7beuzxu4umn5b2i</a> </span>
<a target="_blank" rel="noopener" href="https://web.archive.org/web/20200206070453/http://europepmc.org/backend/ptpmcrender.fcgi?accid=PMC5082409&amp;blobtype=pdf" title="fulltext PDF download" data-goatcounter-click="serp-fulltext" data-goatcounter-title="serp-fulltext"> <button class="ui simple right pointing dropdown compact black labeled icon button serp-button"> <i class="icon ia-icon"></i> Web Archive [PDF] <div class="menu fulltext-thumbnail"> <img src="https://blobs.fatcat.wiki/thumbnail/pdf/51/5d/515dc2553a702cb70ed8a16c79edbadfa3e82574.180px.jpg" alt="fulltext thumbnail" loading="lazy"> </div> </button> </a> <a target="_blank" rel="external noopener noreferrer" href="https://doi.org/10.1111/jcmm.12890"> <button class="ui left aligned compact blue labeled icon button serp-button"> <i class="unlock alternate icon" style="background-color: #fb971f;"></i> Publisher / doi.org </button> </a> <a target="_blank" rel="external noopener" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5082409" title="pubmed link"> <button class="ui compact blue labeled icon button serp-button"> <i class="file alternate outline icon"></i> pubmed.gov </button> </a>