Hydrogen peroxide-mediated nuclear factor κB activation in both liver and tumor cells during initial stages of hepatic metastasis
Hydrogen peroxide-mediated nuclear factor κB activation in both liver and tumor cells during initial stages of hepatic metastasis
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DOI：
10.1111/j.1349-7006.2008.00856.x
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发表时间：
2008-08-01
期刊：
影响因子：
5.7
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
--
作者：
Kobayashi, Yuki;Nishikawa, Makiya;Hashida, Mitsuru
参与肿瘤转移的多种因素均受转录因子核因子 kappa B (NF-kappa B) 的调节。由于 NF-κB 激活可能有助于肝转移的建立，因此在肝转移小鼠模型中分别评估了其在肝细胞和肿瘤细胞中的激活。 pNF-kappa B-Luc 是一种取决于 NF-kappa B 活性的萤火虫荧光素酶表达质粒 DNA，通过基于流体动力学的程序注射到小鼠尾静脉中，这是一种将基因转移到 BALB/c 雄性小鼠肝脏的成熟方法。门静脉内接种小鼠结肠腺癌结肠26细胞后，肝脏中的荧光素酶活性显着增加，但腹膜巨噬细胞则没有增加，这表明当肿瘤细胞进入肝循环时，肝细胞中的NF-κB被激活。然后，接种稳定转染pNF-κ B-Luc的colon26细胞。当将colon26/NF kappa B-Luc细胞接种到BALB/c雄性小鼠的门静脉中时，萤火虫荧光素酶活性（肿瘤细胞中NF-kappa B活性的指标）显着增加。注射过氧化氢酶衍生物可显着抑制肝脏和肿瘤细胞中的 NF-κB 激活，据报道过氧化氢酶衍生物可抑制肿瘤细胞的肝转移。这些发现首次表明，NF-kappa B（调节参与肿瘤转移的各种分子表达的关键因子）在肿瘤转移的初始阶段通过过氧化氢介导的途径在肝脏和肿瘤细胞中被激活。因此，去除过氧化氢将是治疗肝转移的一种有前途的方法。 （癌症科学 2008 年；99：1546-1552）
Various factors involved in tumor metastasis are regulated by the transcription factor nuclear factor kappa B (NF-kappa B). Because NF-kappa B activation may contribute to establishment of hepatic metastasis, its activation in liver cells and tumor cells was separately evaluated in a mouse model of hepatic metastasis. pNF-kappa B-Luc, a firefly luciferase-expressing plasmid DNA depending on the NF-kappa B activity, was injected into the tail vein of mice by the hydrodynamics-based procedure, a well-established method for gene transfer to BALB/c male mouse liver. The luciferase activity in the liver was significantly increased by an intraportal inoculation of murine adenocarcinoma colon26 cells, but not of peritoneal macrophages, suggesting that the NF-kappa B in liver cells is activated when tumor cells enter the hepatic circulation. Then, colon26 cells stably transfected with pNF-kappa B-Luc were inoculated. The firefly luciferase activity, an indicator of NF-kappa B activity in tumor cells, was significantly increased when colon26/NF kappa B-Luc cells were inoculated into the portal vein of BALB/c male mice. The NF-kappa B activation in both liver and tumor cells was significantly inhibited by injection of catalase derivatives, which have been reported to inhibit hepatic metastasis of tumor cells. These findings indicate for the first time that NF-kappa B, a key agent regulating the expression of various molecules involved in tumor metastasis, is activated in both liver and tumor cells during the initial stages of tumor metastasis through a hydrogen peroxide mediated pathway. Thus, the removal of hydrogen peroxide will be a promising approach to treating hepatic metastasis. (Cancer Sci 2008; 99: 1546-1552)