兰克尔
骨保护素
嫌色细胞
骨转移
转移
癌症研究
秩配基
受体
细胞迁移
细胞
病理
医学
生物
激活剂(遗传学)
内科学
清除单元格
癌症
肾细胞癌
遗传学
作者
Shuji Mikami,Ken Ichi Katsube,Mototsugu Oya,Masaru Ishida,Takeo Kosaka,Ryuichi Mizuno,Satsuki Mochizuki,Tohru Ikeda,Makio Mukai,Yasunori Okada
摘要
Abstract Receptor activator of NF‐κB ligand (RANKL) and its receptor, receptor activator of NF‐κB (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 © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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