Optimized Mouse Model for the Imaging of Tumor Metastasis upon Experimental Therapy
Optimized Mouse Model for the Imaging of Tumor Metastasis upon Experimental Therapy
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DOI：
10.1371/journal.pone.0026810
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发表时间：
2011-11-03
期刊：
影响因子：
3.7
通讯作者：
Pesonen, Sari
中科院分区：
文献类型：
--
作者：
Lavilla-Alonso, Sergio;Abo-Ramadan, Usama;Pesonen, Sari
新癌症治疗的开发越来越关注癌症组织与其微环境的关系。开发新抗癌疗法的一个主要障碍是缺乏相关的动物模型来重现从早期原发肿瘤到成熟转移组织的发展所涉及的疾病进展的所有事件。为此，我们开发了一种易于成像的结直肠癌小鼠模型，其特征是源自脾内原发肿瘤的自发性肝转移的高度可重复的形成。我们优化了几个实验变量，发现细胞系和遗传背景的正确选择以及受体小鼠的年龄对于建立有用的模型系统至关重要。在一组测试的结直肠癌细胞系中，发现上皮癌 HT29 细胞系在产生同质肿瘤生长和转移方面是最合适的。在我们看来，125 天或以上的 SCID 小鼠最适合支持脾脏植入后 HT29 肿瘤的持续生长，然后可重复地转移至肝脏。磁共振成像 (MRI) 方案针对该小鼠模型进行了优化，并被证明是分析实验疗法抗肿瘤效果的强大方法。具体来说，我们使用该系统成功地通过 MRI 监测脾内施用溶瘤腺病毒疗法在减少内脏肿瘤负荷和肝转移发展方面的功效进行了验证。总之，我们开发了一种高度优化的结直肠癌肝转移小鼠模型，该模型可以检测全身水平的肿瘤负荷，并能够准确地针对癌症进展和转移发展的不同阶段进行治疗干预。
Development of new cancer treatments focuses increasingly on the relation of cancer tissue with its microenvironment. A major obstacle for the development of new anti-cancer therapies has been the lack of relevant animal models that would reproduce all the events involved in disease progression from the early-stage primary tumor until the development of mature metastatic tissue. To this end, we have developed a readily imageable mouse model of colorectal cancer featuring highly reproducible formation of spontaneous liver metastases derived from intrasplenic primary tumors. We optimized several experimental variables, and found that the correct choice of cell line and the genetic background, as well as the age of the recipient mice, were critical for establishing a useful model system. Among a panel of colorectal cancer cell lines tested, the epithelial carcinoma HT29 line was found to be the most suitable in terms of producing homogeneous tumor growth and metastases. In our hands, SCID mice at the age of 125 days or older were the most suitable in supporting consistent HT29 tumor growth after splenic implantation followed by reproducible metastasis to the liver. A magnetic resonance imaging (MRI) protocol was optimized for use with this mouse model, and demonstrated to be a powerful method for analyzing the antitumor effects of an experimental therapy. Specifically, we used this system to with success to verify by MRI monitoring the efficacy of an intrasplenically administered oncolytic adenovirus therapy in reducing visceral tumor load and development of liver metastases. In summary, we have developed a highly optimized mouse model for liver metastasis of colorectal cancer, which allows detection of the tumor load at the whole body level and enables an accurate timing of therapeutic interventions to target different stages of cancer progression and metastatic development.