Manni Isabella, de Latouliere Luisa, Gurtner Aymone, Piaggio Giulia
UOSD SAFU, Department of Research, Diagnosis and Innovative Technologies, IRCCS-Regina Elena National Cancer Institute, Rome, Italy.
Front Pharmacol. 2019 Mar 15;10:235. doi: 10.3389/fphar.2019.00235. eCollection 2019.
Preclinical animal models are valuable tools to improve treatments of malignant diseases, being an intermediate step of experimentation between cell culture and human clinical trials. Among different animal models frequently used in cancer research are mouse and, more recently, zebrafish models. Indeed, most of the cellular pathways are highly conserved between human, mouse and zebrafish, thus rendering these models very attractive. Recently, several transgenic reporter mice and zebrafishes have been generated in which the luciferase reporter gene are placed under the control of a promoter whose activity is strictly related to specific cancer cellular processes. Other mouse models have been generated by the cDNA luciferase knockin in the locus of a gene whose expression/activity has increased in cancer. Using BioLuminescence Imaging (BLI), we have now the opportunity to spatiotemporal visualize cell behaviors, among which proliferation, apoptosis, migration and immune responses, in any body district in living animal in a time frame process. We provide here a review of the available models to visualized cancer and cancer-associated events in living animals by BLI and as they have been successful in identifying new stages of early tumor progression, new interactions between different tissues and new therapeutic responsiveness.
临床前动物模型是改善恶性疾病治疗的宝贵工具,是细胞培养和人体临床试验之间的中间实验步骤。在癌症研究中常用的不同动物模型包括小鼠,以及最近的斑马鱼模型。事实上,人类、小鼠和斑马鱼之间的大多数细胞通路高度保守,因此这些模型非常有吸引力。最近,已经产生了几种转基因报告小鼠和斑马鱼,其中荧光素酶报告基因置于启动子的控制之下,该启动子的活性与特定的癌症细胞过程密切相关。其他小鼠模型是通过将cDNA荧光素酶敲入癌症中表达/活性增加的基因位点而产生的。利用生物发光成像(BLI),我们现在有机会在时间框架过程中对活体动物任何身体部位的细胞行为进行时空可视化,其中包括增殖、凋亡、迁移和免疫反应。我们在此综述了通过BLI可视化活体动物癌症和癌症相关事件的可用模型,以及它们如何成功识别早期肿瘤进展的新阶段、不同组织之间的新相互作用和新的治疗反应性。