Promising xenograft animal model recapitulating the features of human pancreatic cancer
Promising xenograft animal model recapitulating the features of human pancreatic cancer
复制标题
有前途的异种移植动物模型再现了人类胰腺癌的特征
DOI：
10.3748/wjg.v26.i32.4802
复制
发表时间：
2020-08-28
影响因子：
4.3
通讯作者：
Wang, Yao-He
中科院分区：
文献类型：
--
作者：
Miao, Jin-Xin;Wang, Jian-Yao;Wang, Yao-He
背景技术基质中的多部位转移和促纤维增生反应是人类胰腺癌（PC）的关键特征。目前还没有简单可靠的动物模型可以模仿这些特征来进行准确的疾病建模。目的 创建一种新的异种移植动物模型，能够忠实地再现人类 PC 的特征。方法 创建白细胞介素 2 受体亚基 γ (IL2RG) 基因敲除叙利亚仓鼠并对其进行表征。将一组人类 PC 细胞系皮下或原位移植到 IL2RG 敲除的叙利亚仓鼠和严重免疫缺陷小鼠中。比较随时间推移的肿瘤生长、局部侵袭、远端器官转移、组织病理学以及肿瘤细胞和基质的分子变化。结果 IL2RG 基因敲除的叙利亚仓鼠（命名为 ZZU001）表现出免疫缺陷表型和功能。 ZZU001仓鼠忠实地再现了人类PC的大部分特征，特别是它们在多个部位出现了转移。源自 ZZU001 仓鼠的 PC 组织在基质和上皮间充质转化表型中显示出促纤维增生反应，而源自免疫缺陷小鼠的 PC 组织则不表现出此类特征。结论 与免疫缺陷小鼠相比，移植人 PC 细胞的 ZZU001 仓鼠是一种更优秀的动物模型。 ZZU001仓鼠可以作为一种有价值的动物模型，用于更好地了解肿瘤发生和转移的分子机制以及针对人类PC的新药物的评估。
BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer (PC). There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling. AIM To create a new xenograft animal model that can faithfully recapitulate the features of human PC. METHODS Interleukin 2 receptor subunit gamma (IL2RG) gene knockout Syrian hamster was created and characterized. A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically. Tumor growth, local invasion, remote organ metastasis, histopathology, and molecular alterations of tumor cells and stroma were compared over time. RESULTS The Syrian hamster with IL2RG gene knockout (named ZZU001) demonstrated an immune-deficient phenotype and function. ZZU001 hamsters faithfully recapitulated most features of human PC, in particular, they developed metastasis at multiple sites. PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes, whereas PC tissues derived from immune-deficient mice did not present such features. CONCLUSION ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice. ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.