Reg IV enhances peritoneal metastasis in gastric carcinomas
Reg IV enhances peritoneal metastasis in gastric carcinomas
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DOI：
10.1111/j.1365-2184.2008.00577.x
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发表时间：
2009-02-01
影响因子：
8.5
通讯作者：
Yasui, W.
中科院分区：
文献类型：
--
作者：
Kuniyasu, H.;Oue, N.;Yasui, W.
使用Reg IV转染的人胃癌细胞（MKN28-R1、MKN28-R2、TMK1-R1）、对照转染子（MKN28-R0、TMK1-R0）和REG4敲低的MKN45细胞在体外和裸鼠中进行检查。 Reg IV 转染子中 Reg IV 的表达和分泌增加，BCL-2、BCL-XL、生存素、磷酸化 AKT 和磷酸化 EGFR 水平增加，一氧化氮诱导的细胞凋亡减少，而在敲低细胞中这些情况被消除。在小鼠模型中，Reg IV 转染子中发现腹膜肿瘤的数量和大小增加，细胞凋亡减少，而这些都被敲低细胞消除了。接种 Reg IV 转染子的小鼠的存活率恶化，但接种 Reg IV 敲低细胞的小鼠的存活率有所改善。在Reg IV转染子接种的小鼠中，腹腔灌洗液中Reg IV蛋白的水平增加，但在Reg IV敲低细胞接种的小鼠中降低。在转移性人类胃癌中，腹膜转移病例的 Reg IV 阳性率高于阴性病例。在人胃癌患者的腹腔灌洗液中检测到Reg IV，并通过逆转录聚合酶链反应检测其灌洗液中的角蛋白mRNA。总的来说，Reg IV 可能会加速胃癌的腹膜转移。灌洗液中的 Reg IV 可能是腹膜转移的良好标志物。
The role of Regenerating (Reg) IV on peritoneal metastasis was examined in gastric cancer using.Reg IV-transfected human gastric cancer cells (MKN28-R1, MKN28-R2, TMK1-R1), control transfectants (MKN28-R0, TMK1-R0), and REG4-knocked down MKN45 cells were examined in in vitro and in nude mice peritoneal metastasis models.Increase of expression and secretion of Reg IV, and levels of BCL-2, BCL-XL,survivin, phosphorylated AKT, and phosphorylated EGFR, and decrease of nitric oxide-induced apoptosis were found in Reg IV-transfectants, whereas those were abrogated in the knockdown cells. In mice models, increased number and size of peritoneal tumors and decreased apoptosis were found in Reg IV-transfectants, whereas those were abrogated by the knockdown cells. Mice survivals were worsened in Reg IV-transfectants-inoculated mice, but were improved in Reg IV-knockdown cell-inoculated mice. Levels of Reg IV protein in peritoneal lavage fluids increased in Reg IV-transfectants inoculated mice, but decreased in Reg IV-knockdown cell inoculated mice. In metastasized human gastric cancers, Reg IV positivity in peritoneum-metastasis cases was higher than those in negative cases. Reg IV was detected in peritoneal lavage fluids from human gastric cancer patients, in whose lavages keratin mRNA was detected by reverse transcriptase-polymerase chain reaction. Collectively, Reg IV might accelerate peritoneal metastasis in gastric cancer. Reg IV in lavage fluids might be a good marker for peritoneal metastasis.