Promising xenograft animal model recapitulating the features of human pancreatic cancer

查看全文 作　　者：Jin-Xin [1,2]Miao;Jian-Yao [1]Wang;Hao-Ze [1]Li;Hao-Ran [1]Guo;Louisa S Chard [3]Dunmall;Zhong-Xian [1]Zhang;Zhen-Guo [1]Cheng;Dong-Ling [1]Gao;Jian-Zeng [4]Dong;Zhong-De [5]Wang;Yao-He [3]Wang

机构地区：[1]Sino-British Research Centre for Molecular Oncology,National Centre for International Research in Cell and Gene Therapy,Academy of Medical Sciences,Zhengzhou University,Zhengzhou 450000,Henan Province,China;[2]Academy of Chinese Medical Sciences,Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China;[3]Centre for Biomarkers and Biotherapeutics,Barts Cancer Institute,Queen Mary University of London,London EC1M6BQ,United Kingdom;[4]Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing 100029,China;[5]Department of Animal Dairy,and Veterinary Sciences,Utah State University,Logan UT 84341,United States

出　　处：《World Journal of Gastroenterology》索引2020年第26卷第32期,共15页

基　　金：Supported by the National Key R and D Program of China,No.2016YFE0200800;Nature Sciences Foundation of China,No.81771776;Nature Sciences Foundation of China,No.U1704282;Medical Research of Council,No.MR/M015696/1. 摘　　要：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. 关键词：Pancreatic cancer Xenotrans plantation Syrian hamster IL-2 receptor gamma chain gene METASTASIS Animal model

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Promising xenograft animal model recapitulating the features of human pancreatic cancer

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