Gutwein Paul, Schramme Anja, Sinke Nina, Abdel-Bakky Mohamed Sadek, Voss Beren, Obermüller Nicholas, Doberstein Kai, Koziolek Michael, Fritzsche Florian, Johannsen Manfred, Jung Klaus, Schaider Helmut, Altevogt Peter, Ludwig Andreas, Pfeilschifter Josef, Kristiansen Glen
Pharmazentrum Frankfurt/ZAFES, Klinikum der Johann Wolfgang Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60590 Frankfurt am Main, Germany.
Eur J Cancer. 2009 Feb;45(3):478-89. doi: 10.1016/j.ejca.2008.10.023. Epub 2008 Dec 11.
The aim of our study was to analyse the expression of CXCL16, ADAM10 and CXCR6 in renal cell carcinoma (RCC) tissue and to correlate the expression pattern with clinicopathologic data, including patient survival. Furthermore, we investigated CXCL16, ADAM10 and CXCR6 expressions by FACS, immunofluorescence and ELISA analysis in renal carcinoma cell lines. Our immunohistochemical analysis on tissue microarray of renal cancer samples of 104 patients revealed that ADAM10 correlated significantly with tumour stage, pathological nodal status, M status and lymphangiosis carcinomatosa. CXCL16, CXCR6 and ADAM10 were significantly increased in papillary carcinomas. Importantly, high levels of CXCL16 expression in renal cancer tissue correlated with better survival of patients, and CXCL16 correlated inversely to the tumour stage. In addition, inhibition of CXCL16 induced the migration of renal cancer cells assuming an anti-migratory function of transmembrane CXCL16. Taken together, our data demonstrate that downregulation of CXCL16 plays an important role in renal cancer development and progression, and that CXCL16 in RCC is an independent prognostic marker for better patient survival.
我们研究的目的是分析肾细胞癌(RCC)组织中CXCL16、ADAM10和CXCR6的表达,并将表达模式与临床病理数据(包括患者生存率)相关联。此外,我们通过流式细胞术(FACS)、免疫荧光和酶联免疫吸附测定(ELISA)分析了肾癌细胞系中CXCL16、ADAM10和CXCR6的表达。我们对104例患者的肾癌样本组织芯片进行的免疫组织化学分析显示,ADAM10与肿瘤分期、病理淋巴结状态、M状态和癌性淋巴管炎显著相关。CXCL16、CXCR6和ADAM10在乳头状癌中显著升高。重要的是,肾癌组织中CXCL16的高表达与患者更好的生存率相关,且CXCL16与肿瘤分期呈负相关。此外,CXCL16的抑制诱导肾癌细胞迁移,提示跨膜CXCL16具有抗迁移功能。综上所述,我们的数据表明CXCL16的下调在肾癌的发生和发展中起重要作用,且肾细胞癌中的CXCL16是患者更好生存的独立预后标志物。