Division of Genetics, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.
Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kanazawa, Japan.
Methods Mol Biol. 2023;2691:19-30. doi: 10.1007/978-1-0716-3331-1_2.
It has been established that the accumulation of driver gene mutations causes malignant progression of colorectal cancer (CRC) through positive selection and clonal expansion, similar to Darwin's evolution. Following this multistep tumorigenesis concept, we previously showed the specific mutation patterns for each process of malignant progression, including submucosal invasion, epithelial mesenchymal transition (EMT), intravasation, and metastasis, using genetically engineered mouse and organoid models. However, we also found that certain populations of cancer-derived organoid cells lost malignant characteristics of metastatic ability, although driver mutations were not impaired, and such subpopulations were eliminated from the tumor tissues by negative selection. These organoid model studies have contributed to our understanding of the cancer evolution mechanism. We herein report the in vitro and in vivo experimental protocols to investigate the survival, growth, and metastatic ability of intestinal tumor-derived organoids. The model system will be useful for basic research as well as the development of clinical strategies.
已经证实，驱动基因突变的积累通过正选择和克隆扩增导致结直肠癌（CRC）的恶性进展，类似于达尔文的进化。基于这一多步骤肿瘤发生概念，我们之前使用基因工程小鼠和类器官模型显示了每个恶性进展过程的特定突变模式，包括黏膜下浸润、上皮间质转化（EMT）、浸润和转移。然而，我们还发现，尽管驱动突变未受损，但某些癌症衍生的类器官细胞群体失去了转移能力的恶性特征，并且这些亚群通过负选择从肿瘤组织中消除。这些类器官模型研究有助于我们理解癌症进化机制。本文报告了用于研究肠肿瘤衍生类器官的存活、生长和转移能力的体外和体内实验方案。该模型系统将有助于基础研究以及临床策略的发展。
