Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas
Increased RANKL expression is related to tumour migration and metastasis of renal cell carcinomas
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DOI：
10.1002/path.2567
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发表时间：
2009-08-01
影响因子：
7.3
通讯作者：
Okada, Yasunori
中科院分区：
文献类型：
--
作者：
Mikami, Shuji;Katsube, Ken-ichi;Okada, Yasunori
核因子-κ B配体受体激活因子（RANKL）及其受体--核因子-κ B受体激活因子（RANK）在破骨细胞生成中起关键作用，骨保护素（OPG）作为RANKL的诱饵受体。我们研究了RANKL-RANK-OPG系统在肾细胞癌（RCC）中的作用，RCC经常转移到骨。实时定量PCR显示透明细胞型RCC中RANKL mRNA的表达高于乳头状和嫌色细胞型RCC。透明细胞型RCC中RANKL蛋白表达水平高于乳头状型和嫌色细胞型RCC，与肿瘤原发分期和远处转移呈正相关。RANK、OPG的表达水平与肾细胞癌的组织学类型无关。RANKL和RANK表达在骨和其他器官的转移性RCC中观察到，表明它们在骨和其他器官的转移中起作用。重组RANKL蛋白在体外刺激透明细胞RCC细胞系Caki-1的迁移，而这种增强的迁移被重组OPG蛋白给药抑制。多因素考克斯分析显示，RANKL和RANK表达升高和OPG表达降低是复发、骨转移和预后不良的独立预测因子。这些数据表明，RANKL-RANK-OPG系统不仅参与RCC的骨转移，还通过刺激癌细胞迁移参与转移至其他器官。版权所有（C）2009大不列颠和爱尔兰病理学会。出版社：John Wiley & Sons，Ltd
Receptor activator of NF-kappa B ligand (RANKL) and its receptor, receptor activator of NF-kappa B (RANK), play a key role in osteoclastogenesis, and osteoprotegerin (OPG) acts as a decoy receptor for RANKL. We investigated the role of the RANKL-RANK-OPG system in renal cell carcinomas (RCCs), which frequently metastasize to bones. Real-time quantitative PCR revealed that RANKL mRNA expression was higher in clear cell RCCs than in papillary and chromophobe RCCs. Similarly, RANKL protein expression level in clear cell RCCs was higher than that in papillary and chromophobe RCCs, showing positive correlations with the primary tumour stage and distant metastasis. There was no significant association between the expression level of RANK, OPG and histological subtypes of RCC. RANKL and RANK expression was observed in metastatic RCCs in the bone and other organs, suggesting that they play a role in metastasis to the bone and other organs. Recombinant RANKL protein stimulated migration of a clear cell RCC cell line, Caki-1, in vitro, and this enhanced migration was inhibited by the administration of recombinant OPG protein. Furthermore, multivariate Cox analysis revealed that elevated RANKL and RANK expression with low-OPG expression was a significant and independent predictor of recurrence, bone metastasis and a poor prognosis. These data suggest that the RANKL-RANK-OPG system is involved not only in the bone metastasis of RCCs but also in metastasis to other organs through the stimulation of cancer cell migration. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.