The association of CXCR3 and renal cell carcinoma metastasis.
The association of CXCR3 and renal cell carcinoma metastasis.
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DOI：
10.1016/j.juro.2014.01.100
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发表时间：
2014-08
期刊：
影响因子：
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通讯作者：
T. Utsumi;T. Suyama;Y. Imamura;M. Fuse;S. Sakamoto;N. Nihei;T. Ueda;Hiroyoshi Suzuki;N. Seki;T. Ichikawa
中科院分区：
文献类型：
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作者：
T. Utsumi;T. Suyama;Y. Imamura;M. Fuse;S. Sakamoto;N. Nihei;T. Ueda;Hiroyoshi Suzuki;N. Seki;T. Ichikawa
目的肾细胞癌表达CXCR3，但CXCR3在肾癌中的作用尚不清楚。本研究旨在探讨CXCR3在肾癌中的作用，并探讨CXCR3的调控因子。材料与方法收集2000年至2011年在千叶大学附属医院接受根治性肾切除术的日本患者的肾透明细胞癌临床标本及相应的正常肾组织标本56例。以肾细胞癌细胞系786-O、ACHN和Caki-1为研究对象。检测CXCR3及其剪接变异体的表达谱。结果肾细胞癌组织中CXCR3及其配体的表达水平明显高于相应的正常肾组织。结果肾细胞癌组织中CXCR3及其配体的表达水平明显高于正常肾组织。肾细胞癌组织中CXCR3-A/CXCR3-B的比值是正常肾组织的1.5倍。CXCL10诱导786-O细胞迁移和侵袭，并被中和抗体抑制。CXCL10可上调磷酸化RhoA和前/活性基质金属蛋白酶-9的表达。在临床标本中，CXCR3和CXCR3-A在转移性癌组织中的表达明显高于非转移性癌组织。最后，CXCR3-A和HIF-1α在临床标本中的表达显著相关。在CoCl2处理的786-O细胞中，CXCR3和HIF-1α的表达分别上调了4.5倍和2.2倍。CXCR3的表达可能受低氧的调节。
PurposeRenal cell carcinoma expresses CXCR3 but the function of CXCR3 in renal cell carcinoma has not been clarified. We explored the function of CXCR3 in renal cell carcinoma and investigated CXCR3 regulating factors.Materials and MethodsWe obtained 56 clinical samples of clear cell renal cell carcinoma and corresponding normal renal tissue samples from the surgical specimens of Japanese patients who underwent radical nephrectomy at Chiba University Hospital between 2000 and 2011. As renal cell carcinoma cell lines, we used 786-O, ACHN and Caki-1. The expression profiles of CXCR3 and its splice variants were examined. For functional analyses 786-O and interferon-γ inducible 10 kDa protein or IP-10 (CXCL10) were selected as representatives.ResultsCXCR3 and its ligands were abundant in renal cell carcinoma samples compared to corresponding normal kidney samples. The CXCR3-A-to-CXCR3-B ratio was 1.5 times higher in renal cell carcinoma samples than in normal kidney samples. CXCL10 treatment induced 786-O cell migration and invasion, and these effects were inhibited by neutralizing antibody. Phosphorylated RhoA and pro/active matrix metalloproteinase-9 expression was up-regulated by CXCL10 treatment. In clinical samples CXCR3 and CXCR3-A expression was significantly higher in metastatic than in nonmetastatic carcinoma samples. Finally, the expression of CXCR3-A and HIF-1α correlated significantly in clinical samples. In 786-O treatment with CoCl2up-regulated CXCR3 and HIF-1α expression 4.5 and 2.2-fold, respectively.ConclusionsWe determined the association of CXCR3 and renal cell carcinoma metastasis. CXCR3 expression may be regulated by hypoxia.