Open AccessTNF ‐α augments CXCR 2 and CXCR 3 to promote progression of renal cell carcinoma
Author(s) -
Sun KuangHui,
Sun GuangHuan,
Wu YiChing,
Ko BaiJiun,
Hsu HuiTzu,
Wu ShengTang
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12890
Subject(s) - cancer research , chemokine receptor , chemokine , biology , gene knockdown , gene silencing , tumor necrosis factor alpha , tumor progression , immunology , cancer , inflammation , cell culture , biochemistry , gene , genetics
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 ‐α) are associated with tumour progression and an anti‐ TNF ‐α 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 ‐α‐promoted progression of RCC remains unclear. In this study, TNF ‐α was found to enhance the migration, invasion and epithelial‐mesenchymal transition ( EMT ) of RCC cells. To further investigate the molecular mechanism of TNF ‐α 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 ‐α significantly increased the expressions of CXCR 2 and CXCR 3 and their related ligands in RCC cells. Subsequently, we used a lentiviral sh RNA system to knockdown the expression of CXCR 2 and/or CXCR 3 in RCC cells. CXCR 2 and CXCR 3 silencing inhibited the induction of Slug and ZEB ‐1 with TNF ‐α treatment of RCC cells. In addition, the knockdown of both CXCR 2 and CXCR 3 resulted in a greater decrease in cell migration, invasion and clonogenic ability compared with either CXCR 2 or CXCR 3 knockdown alone. Moreover, CXCR 2 and CXCR 3 silencing significantly reduced the sphere‐forming ability of RCC cells. High expression levels of CXCR 2 and CXCR 3 in cancer tissues correlated with tumour progression of renal cell carcinoma. These findings suggest that TNF ‐α augments CXCR 2 and CXCR 3 to promote the progression of renal cell carcinoma leading to a poor prognosis.