A tree shrew glioblastoma model recapitulates features of human glioblastoma
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Yaohui Tong1,2,*, Junjun Hao3,*, Qiu Tu2,4,*, Hualin Yu5, Lanzhen Yan2,6, Yuan Li2,4,7, Longbao Lv6, Fei Wang5, Antonio Iavarone8, Xudong Zhao2,6
1School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, China
2Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China
3State Key Lab of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
4Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
5Department of Neurological Surgery, The First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, 650032, China
6Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
7Kunming University of Science and Technology, Kunming, Yunnan, 650500, China
8Institute for Cancer Genetics, Columbia University, New York, New York 10032, USA
*These authors contributed equally to this work
Xudong Zhao, email: email@example.com
Keywords: glioblastoma, animal model, tree shrew, P53
Received: June 03, 2016 Accepted: January 16, 2017 Published: February 09, 2017
Tupaia belangeri (tree shrew), an animal species whose genome has significantly higher similarity to primates than rodents, has been used in biomedical research. To generate animal models that reproduce the human tumors more faithfully than rodents, we present the first report of a cancer model mimicking human tumor genetics in tree shrew. By engineering a lentiviral system for the transduction of mutant H-Ras and a shRNA against tree shrew p53, we successfully generated malignant glioma in tree shrew. The tree shrew glioma exhibited aggressive behavior and a relatively short latency, and markedly reduced animal survival. Remarkably, the biological features of human high-grade glioma (necrosis, microvascular proliferation, pseudopalisading) were all present in tree shrew glioma. Furthermore, genetic analysis of tree shrew glioma revealed that the tumors were clustered within the mesenchymal subgroup of human glioblastoma multiforme. Compared with the corresponding mouse glioma, tree shrew gliomas were markedly more similar to human glioblastoma at gene expression profile. The tree shrew glioma model provides colleagues working in the field of gliomas and cancer in general with a more accurate animal model.
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