Porcine Models of Pancreatic Cancer: Current Status and Future

The KRASG12D and TP53R172H mutations are the leading causes of pancreatic cancer, with the third deadliest cancer mortality rate. Majority of the pancreatic cancer research utilizes mouse models. Our lab is currently studying porcine as a suitable model to study pancreatic cancer due to the comparative anatomy and genomic similarities between humans and porcine. Our first approach to develop the porcine pancreatic cancer model was to orthotopically implant the transformed and mutated primary pig pancreatic epithelial cells into the pig pancreas. The second approach was using the Oncopig model with KRASG12D and TP53R172H genetic mutations. The mutated genes were expressed by injecting adenovirus with Cre recombinase to develop tumors. Hematoxylin and Eosin staining, immunohistochemistry, plasmid, and RNA isolation were used to study the porcine pancreas before and after the tumor induction. Results showed that humans and porcine have similar histological characteristics showing comprising islets, ducts, and acinar cells. For the orthotopic model, after two weeks of orthotopic implantation, there were signs of pancreatitis and some evidence of tumor-like cells, but not tumors. Some signs were the formation of acinar to ductal metaplasia, massive immune cell responses, and vimentin expression in the regions of desmoplasia. Our results showed that the Oncopigs did generate pancreatic tumors successfully and are currently being characterized for future use, and the orthotopic model showed promising results. However, implanted tumor cells will be given additional help to allow them to survive from host immune response by over-expressing PD-L1 on the implanted tumor cells surface.https://digitalcommons.unmc.edu/surp2022/1041/thumbnail.jp