The Effects of Epidermal Growth Factor Receptor Activation and Attenuation of the TGFβ Pathway in an Orthotopic Model of Colon Cancer
The Effects of Epidermal Growth Factor Receptor Activation and Attenuation of the TGFβ Pathway in an Orthotopic Model of Colon Cancer
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DOI：
10.1016/j.jss.2009.02.002
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发表时间：
2009-10-01
影响因子：
2.2
通讯作者：
Rajput, Ashwani
中科院分区：
文献类型：
--
作者：
Ongchin, Melanie;Sharratt, Elizabeth;Rajput, Ashwani
背景资料。结直肠癌是癌症相关死亡的第二大原因，大多数死亡是由转移引起的。很少有活体模型允许研究复杂的转移过程。本研究的目的是在原位模型中确定表皮生长因子受体的激活和转化生长因子β途径的减弱对人结肠癌细胞系FET的影响。利用FET，构建了FETα、FETαdN-RII和FETDNRII细胞。将肿瘤原位移植到BALB/c裸小鼠的结肠上。7wk后，处死小鼠，取出脏器进行检查。所有细胞系均表现为原发侵袭。与FETαDNRII和FETDNRII相比，FETα转移较弱，后者分别显示肺和肝脏的转移。表皮生长因子受体(EGFR)的激活可以将非致瘤细胞株转化为致瘤但不转移的细胞系。随着转化生长因子β信号的减弱，肿瘤发生线发生转移。在转化生长因子β抑制系中失去EGFR激活导致转移负荷降低，但重要的是，改变了器官亲和性归巢从肺到肝。因此，这些体内研究表明，EGFR激活和转化生长因子β信号通路在肿瘤的发生和转移模式中发挥作用。(C)2009年，爱思唯尔公司出版。
Background. Colorectal cancer is the second leading cause of cancer related mortality, with a majority of deaths resulting from metastases. Few in vivo models allow for the study of the complex process of metastasis. The purpose of this study was to determine the effects of epidermal growth factor receptor activation and TGF beta pathway attenuation in FET, a weakly tumorigenic human colon cancer cell line, in an orthotopic model.Methods and Results. Using FET, FET alpha, FET alpha DN-RII, and FETDNRII cells were constructed. Tumors were orthotopically implanted onto the colons of BALB/c nude mice. After 7 wk, the mice were euthanized and organs extracted for examination. All cell lines demonstrated primary invasion. FET alpha was weakly metastatic compared with FET alpha DNRII and FETDNRII, which demonstrated metastases to the lung and liver, respectively.Conclusion. Epidermal growth factor receptor (EGFR) activation transforms a nontumorigenic cell line into a tumorigenic but not metastatic one. The tumorigenic line becomes metastatic with the attenuation of TGF beta signaling. Loss of EGFR activation in the TGF beta inhibited line results in a decreased metastatic burden, but importantly, changes the organotropic homing from lung to liver. Thus, these in vivo studies demonstrate that EGFR activation and TGF beta signaling pathways play a role in tumorigenicity and in pattern of metastases. (C) 2009 Published by Elsevier Inc.