Characterization of HCT116 human colon cancer cells in an orthotopic modeld

Characterization of HCT116 human colon cancer cells in an orthotopic modeld
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DOI:
10.1016/j.jss.2007.04.021
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发表时间:
2008-06-15
影响因子:
2.2
通讯作者:
Wang, Jing
Wang, Jing
中科院分区:
医学3区
文献类型:
--
作者:
Rajput, Ashwani;Martin, Ivan Dominguez San;Wang, Jing

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背景结直肠癌转移导致大量癌症相关死亡。这种复杂的多步骤途径的分子机制尚未完全阐明。在没有任何结肠癌转移的转基因模型的情况下,需要满足转移的限速步骤(局部侵袭和远端集落形成)的体内模型系统。本研究的目的是描述人结肠癌细胞系HCT 116在原位模型中的行为。用绿色荧光蛋白转染HCT 116细胞,皮下注射BALB/c裸鼠。一旦建立异种移植物,将其切除并使用显微外科技术原位植入其他32只雄性BALB/c裸鼠中。对动物进行连续成像,并在植入后6-8周处以安乐死。获取组织并进行苏木精和伊红分析。所有32只动物均显示原发性肿瘤生长、侵袭和腹膜扩散。在15/32例(47%)中确定了肝转移,在13/32例(41%)中证实了肺转移。总的来说,19/32(59%)的动物表现出远处转移集落形成。这种结肠癌原位模型实现了转移过程中局部侵袭和远处集落形成的限速步骤。HCT 116人结肠癌细胞系在该体内模型系统中提供了一种工具来剖析参与转移级联的分子机制。(C)2008年爱思唯尔公司All rights reserved.
Background. Colorectal cancer metastases result in a significant number of cancer related deaths. The molecular mechanisms underlying this complex, multi-step pathway are yet to be completely elucidated. In the absence of any transgenic models of colon cancer metastases, an in vivo model system that fulfills the rate limiting steps of metastasis (local invasion and distant colony formation) is needed. The purpose of this study was to characterize the behavior of a human colon cancer cell line, HCT116 in an orthotopic model.Materials and methods. HCT116 cells were transfected with green fluorescence protein and subcutaneously injected into BALB/c nude male mice. Once xenografts were established, they were excised and orthotopically implanted into 32 other male BALB/c nude mice using microsurgical techniques. Animals were serially imaged and euthanized at 6-8 weeks post-implantation. Tissues were procured and processed for hematoxylin and eosin analysis.Results. All 32 animals demonstrated primary tumor growth, invasion and peritoneal spread. Liver metastases were identified in 15/32 (47%), and lung metastases were confirmed in 13/32 (41%). In total, 19/32 (59%) animals demonstrated distant metastatic colony formation.Conclusions. This orthotopic model of colon cancer fulfills the rate limiting steps of local invasion and distant colony formation in the process of metastases. HCT116 human colon cancer cell line in this in vivo model system provides a tool to dissect the molecular mechanism involved in the metastatic cascade. (C) 2008 Elsevier Inc. All rights reserved.