A genetic porcine model of cancer

Lawrence B. Schook; Tiago V. Collares; Wenping Hu; Ying Liang; Fernanda M. Rodrigues; Laurie A. Rund; Kyle M. Schachtschneider; Fabiana K. Seixas; Kuldeep Singh; Kevin D. Wells; Eric M. Walters; Randall S. Prather; Christopher M. Counter

doi:10.1371/journal.pone.0128864

A genetic porcine model of cancer

Lawrence B. Schook
, Tiago V. Collares
, Wenping Hu
, Ying Liang
, Fernanda M. Rodrigues
, Laurie A. Rund
, Kyle M. Schachtschneider
, Fabiana K. Seixas
, Kuldeep Singh
, Kevin D. Wells
, Eric M. Walters
, Randall S. Prather
, Christopher M. Counter

Toxicology and Cancer Biology

Research output: Contribution to journal › Article › peer-review

140 Scopus citations

Abstract

The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic "oncopig" line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer.

Original language	English
Article number	0128864
Journal	PLoS ONE
Volume	10
Issue number	7
DOIs	https://doi.org/10.1371/journal.pone.0128864
State	Published - Jul 1 2015

Bibliographical note

Publisher Copyright:
© 2015 Schook et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

We thank Jiude Mao, and Chad W O’Gorman of the National Swine Resource and Research Center, University of Missouri for their guidance in the construction and production of the transgenic clones, Donita Brady for technical support and discussions, Stacey Adam and Kristy Kuzmuk for foundational results and assistance in conceptualizing this project, and Ning Li for his expertise and discussion regarding the experiments and the transgenic technology. W.H. was supported by the China Scholarship Council (CSC). F.M.R, T.V.C. and F.K.S. were supported by the Brazilian Scholarship Program "Science Without Borders" promoted by the National Counsel of Technological and Scientific Development. Y.L. was supported by the American Cancer Society (ACS178898). C.M.C. was supported by the U.S. National Institutes of Health (CA123031) and the Edward Spiegel Fund of the Lymphoma Foundation. L.B.S. was supported by USDA (AG 58-5438-2-307), the U.S. National Institutes of Health (CA 153132), the Edward William & Jane Marr Gutgsell Foundation, the Cooperative Research Program for Agriculture Science & Technology Development (PJ009103), Rural Development Administration, Republic of Korea. R.S.P. and the National Swine Resource and Research Center was supported by the U.S. National Institutes of Health (U42 OD011140).

Funders	Funder number
Edward Spiegel Fund of the Lymphoma Foundation
Edward William & Jane Marr Gutgsell Foundation	PJ009103
National Institutes of Health (NIH)	CA123031, KL2TR000116
National Institutes of Health (NIH)
American Cancer Society-Michigan Cancer Research Fund	ACS178898
American Cancer Society-Michigan Cancer Research Fund
National Childhood Cancer Registry – National Cancer Institute	R01CA153132
National Childhood Cancer Registry – National Cancer Institute
U.S. Department of Agriculture	AG 58-5438-2-307
U.S. Department of Agriculture
Conselho Nacional de Desenvolvimento Científico e Tecnológico
Rural Development Administration	U42 OD011140
Rural Development Administration
China Scholarship Council

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

General

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10.1371/journal.pone.0128864

Cite this

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abstract = "The large size of the pig and its similarity in anatomy, physiology, metabolism, and genetics to humans make it an ideal platform to develop a genetically defined, large animal model of cancer. To this end, we created a transgenic {"}oncopig{"} line encoding Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R167H, which represent a commonly mutated oncogene and tumor suppressor in human cancers, respectively. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R167H expression, which rendered the cells transformed in culture and tumorigenic when engrafted into immunocompromised mice. Finally, injection of AdCre directly into these oncopigs led to the rapid and reproducible tumor development of mesenchymal origin. Transgenic animals receiving AdGFP (green fluorescent protein) did not have any tumor mass formation or altered histopathology. This oncopig line could thus serve as a genetically malleable model for potentially a wide spectrum of cancers, while controlling for temporal or spatial genesis, which should prove invaluable to studies previously hampered by the lack of a large animal model of cancer.",

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A genetic porcine model of cancer

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

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