Development of a metastatic murine colon cancer model.
Development of a metastatic murine colon cancer model.
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DOI：
10.1016/j.jss.2015.04.030
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发表时间：
2015-11
期刊：
影响因子：
--
通讯作者：
Takabe K
中科院分区：
文献类型：
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作者：
Terracina KP;Aoyagi T;Huang WC;Nagahashi M;Yamada A;Aoki K;Takabe K
现在已经很清楚，癌症和免疫反应之间复杂的相互作用在癌症进展过程中的肿瘤微环境中起着关键作用。随着癌症治疗的新靶点不断被发现和研究，用于临床前研究的小鼠模型需要包括完整的免疫反应，以提供与人类癌症更密切的相关性。我们最近开发了一种改良的同基因原位小鼠结肠癌模型，模拟人类结肠癌的进展，结果一致。肿瘤是用小鼠结肠腺癌细胞系CT26产生的，该细胞系经过修饰，过表达萤火虫荧光素酶基因（CT26-luc1），当使用体内成像系统（IVIS）腹腔注射底物d -荧光素时，可以实时监测肿瘤负荷。小鼠为Balb/C (Harlan)，与CT26-luc1细胞同源。细胞在黏膜下被注射，悬浮在基质中，直接进入盲肠壁。该模型已证实在盲肠内持续植入。体内生物发光可以实时监测肿瘤总负荷。围手术期准备对模型的再现性有显著影响。最后，用生物发光量化的总肿瘤负荷可以估计出体内淋巴结转移。该方法保持了完整的免疫应答，并非常接近临床肿瘤微环境。它有望提供一个宝贵的小鼠转移性结肠癌模型，特别是在针对这些机制的药物开发的临床前研究中。
It has now become clear that the complex interplay of cancer and the immune responses against it plays a critical role in the tumor microenvironment during cancer progression. As new targets for cancer treatment are being discovered and investigated, murine models used for preclinical studies need to include intact immune responses to provide a closer correlation with human cancer. We have recently developed a modified syngeneic orthotopic murine colon cancer model that mimics human colon cancer progression with consistent results. Tumors were created using the murine colon adenocarcinoma cell line, CT26, modified to overexpress the firefly luciferase gene (CT26-luc1), which allowed real time in vivo monitoring of tumor burden when the substrate, D-luciferin, was injected intraperitoneally using the In Vivo Imaging System (IVIS). Mice are Balb/C (Harlan), syngeneic with the CT26-luc1 cells. Cells are injected submucosally, suspended in matrigel, into the cecum wall under direct visualization. The model has demonstrated consistent implantation in the cecum. In vivo bioluminescence allowed real time monitoring of total tumor burden. Perioperative preparation had a significant impact on reproducibility of the model. Finally, total tumor burden quantified with bioluminescence enabled estimation of lymph node metastasis ex vivo. This method maintains an intact immune response and closely approximates the clinical tumor microenvironment. It is expected to provide an invaluable murine metastatic colon cancer model particularly in preclinical studies for drug development targeting those mechanisms.