Oncotarget

Research Papers:

A tree shrew glioblastoma model recapitulates features of human glioblastoma

Yaohui Tong, Junjun Hao, Qiu Tu, Hualin Yu, Lanzhen Yan, Yuan Li, Longbao Lv, Fei Wang, Antonio Iavarone and Xudong Zhao _

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Oncotarget. 2017; 8:17897-17907. https://doi.org/10.18632/oncotarget.15225

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Abstract

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

Correspondence to:

Xudong Zhao, email: zhaoxudong@mail.kiz.ac.cn

Keywords: glioblastoma, animal model, tree shrew, P53

Received: June 03, 2016     Accepted: January 16, 2017     Published: February 09, 2017

ABSTRACT

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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