A Genetic Porcine Model of Cancer

The large size of the pig and 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 a Cre recombinase inducible porcine transgenes encoding KRASG12D and TP53R17H, which represent commonly mutated oncogene and tumor suppressor, respectively, in human cancers. Treatment of cells derived from these oncopigs with the adenovirus encoding Cre (AdCre) led to KRASG12D and TP53R172H 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 development of tumors of mesenchymal origins. Control animals receiving AdGFP (green fluorcescent 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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