A novel function of the receptor for advanced glycation end-products (RAGE) in association with tumorigenesis and tumor differentiation of HCC
A novel function of the receptor for advanced glycation end-products (RAGE) in association with tumorigenesis and tumor differentiation of HCC
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DOI：
10.1245/s10434-007-9698-8
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发表时间：
2008-03-01
影响因子：
3.7
通讯作者：
Aikou, Takashi
中科院分区：
文献类型：
--
作者：
Hiwatashi, Kiyokazu;Ueno, Shinichi;Aikou, Takashi
背景：晚期糖基化终末产物受体（RAGE）的表达对产生各种癌细胞特征的机制有影响。本研究的目的是阐明肝细胞癌（HCC）患者中RAGE表达水平的临床病理相关性，并探讨RAGE表达对HCC特征的影响。方法：采用逆转录聚合酶链反应（RT-PCR）和免疫组织化学方法评估配对的HCC癌组织和非癌组织中RAGE的表达。对定量 RT-PCR 数据与 HCC 患者的临床病理因素进行分析。在体外实验中，比较了 RAGE 转染的 Cos7 和模拟转染的 Cos7 细胞在缺氧条件下的存活率。另外，通过siRNA降低RAGE转染的Cos7细胞中的RAGE水平后，进行了类似的实验。结果：RAGE mRNA在正常肝脏中的表达低于肝炎中的表达，在HCC中表达最高。此外，在 HCC 中，它在高分化和中分化肿瘤中较高，但随着肿瘤去分化为低分化 HCC 而下降。此外，耐缺氧的 HCC 系具有较高水平的 RAGE 表达，并且 RAGE 转染子在缺氧下也表现出显着延长的存活时间。结论：我们的研究结果表明，肿瘤发生早期血液供应较少的 HCC 可能通过缺氧诱导的 RAGE 表达获得对严格缺氧环境的抵抗力。
Background: The expression of the receptor for advanced glycation end products (RAGE) has an impact on the mechanisms giving rise to characteristic features of various cancer cells. The purpose of this study was to elucidate the clinicopathological relevance of the level of RAGE expression in patients with hepatocellular carcinoma (HCC) and to explore the effect of RAGE expression on the characteristic features of HCC.Methods: The expression of RAGE was assessed in paired cancer and noncancerous tissues with HCC, using reverse-transcription polymerase chain reaction (RT-PCR), and immunohistochemistry. The quantitative RT-PCR data were analyzed in association with the clinicopathological factors of the patients with HCC. In in vitro experiments, the survival of RAGE-transfected Cos7 and mock-transfected Cos7 cells was compared under hypoxic conditions. In addition, after reducing RAGE levels in RAGE-transfected Cos7 cells by siRNA, similar experiments were performed.Results: The expression of RAGE mRNA was lower in normal liver than in hepatitis and highest in HCC. Furthermore, in HCC, it was high in well- and moderately differentiated tumors but declined as tumors dedifferentiated to poorly differentiated HCC. Furthermore, HCC lines resistant to hypoxia were found to have higher levels of RAGE expression, and RAGE transfectant also showed significantly prolonged survival under hypoxia.Conclusions: Our results suggest that HCC during the early stage of tumorigenesis with less blood supply may acquire resistance to stringent hypoxic milieu by hypoxia-induced RAGE expression.