Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55
Spontaneous regression of lung metastasis in the absence of tumor necrosis factor receptor p55
复制标题
DOI：
10.1002/ijc.20493
复制
发表时间：
2004-12
影响因子：
6.4
通讯作者：
Y. Tomita;Xiaoqin Yang;Y. Ishida;Y. Nemoto-Sasaki;T. Kondo;M. Oda;G. Watanabe;G. Chaldakov;C. Fujii;N. Mukaida
中科院分区：
文献类型：
--
作者：
Y. Tomita;Xiaoqin Yang;Y. Ishida;Y. Nemoto-Sasaki;T. Kondo;M. Oda;G. Watanabe;G. Chaldakov;C. Fujii;N. Mukaida
为了阐明肿瘤坏死因子（TNF）-α在肺转移中的作用，我们将Renca细胞静脉注射到TNF受体p55缺陷型（TNF-Rp 55 KO）和野生型（WT）小鼠中。显微镜和肉眼可见的转移灶分别出现在肿瘤注射后7天和14天的肺。此外，在WT和TNF-Rp 55 KO小鼠中，转移灶以相似的速率扩大，直到21天，并且肺被转移灶占据。然而，注射后21天后，TNF-Rp 55 KO小鼠的转移灶自发消退，而WT小鼠显示转移灶进行性生长。此外，即使在第26天，当所有WT小鼠死亡时，肺中充满转移灶时，TNF-Rp 55 KO小鼠中的转移灶仍然减小。肿瘤注射后21天后，TNF-Rp 55 KO小鼠中凋亡肿瘤细胞的数量增加。相比之下，与WT小鼠相比，TNF-Rp 55 KO小鼠中的新血管形成较不明显，在肿瘤注射后21天，TNF-Rp 55 KO小鼠中的肝细胞生长因子（HGF）基因受到抑制。因此，TNF-Rp 55介导的信号至少部分通过诱导HGF表达来维持肿瘤新生血管形成，并最终支持肺转移过程。© 2004 Wiley利斯公司
In order to clarify the roles of tumor necrosis factor (TNF)‐α in lung metastasis, we injected Renca cells intravenously into TNF receptor p55‐deficient (TNF‐Rp55 KO) and wild‐type (WT) mice. Microscopic and macroscopic metastasis foci appeared in lungs at 7 and 14 days after the tumor injection, respectively. Moreover, metastasis foci expanded at similar rates in both WT and TNF‐Rp55 KO mice until 21 days, and lungs were occupied with metastasis foci. However, later than 21 days after the injection, metastasis foci spontaneously regressed in TNF‐Rp55 KO mice, whereas WT mice exhibited a progressive growth of metastasis foci. Moreover, metastasis foci remained reduced sizes in TNF‐Rp55 KO mice even at 26 days, when all WT mice died with lungs filled with metastasis foci. Later than 21 days after the tumor injection, the number of apoptotic tumor cells was increased in TNF‐Rp55 KO mice. In contrast, neovascularization was less evident in TNF‐Rp55 KO than WT mice, with depressed hepatocyte growth factor (HGF) gene in TNF‐Rp55 KO mice at 21 days after the tumor injection. Thus, TNF‐Rp55‐mediated signals can maintain tumor neovascularization at least partly by inducing HGF expression, and eventually support lung metastasis process. © 2004 Wiley‐Liss, Inc.