Induction and characterization of pancreatic cancer in a transgenic pig model Journal Article


Authors: Boas, F. E.; Nurili, F.; Bendet, A.; Cheleuitte-Nieves, C.; Basturk, O.; Askan, G.; Michel, A. O.; Monette, S.; Ziv, E.; Sofocleous, C. T.; Maxwell, A. W. P.; Schook, L. B.; Solomon, S. B.; Kelsen, D. P.; Scherz, A.; Yarmohammadi, H.
Article Title: Induction and characterization of pancreatic cancer in a transgenic pig model
Abstract: BACKGROUND: Preclinical testing of new locoregional therapies for pancreatic cancer has been challenging, due to the lack of a suitable large animal model. PURPOSE: To develop and characterize a porcine model of pancreatic cancer. Unlike small animals, pigs have similar physiology, drug dosing, and immune response to humans. Locoregional therapy in pigs can be performed using the same size catheters and devices as in humans. METHODS: The Oncopig is a transgenic pig with Cre-inducible TP53R167H and KRASG12D mutations. In 12 Oncopigs, CT-guided core biopsy of the pancreas was performed. The core biopsy was incubated with an adenoviral vector carrying the Cre recombinase gene. The transformed core biopsy was injected back into the pancreas (head, tail, or both). The resulting tumors (n = 19) were characterized on multi-phase contrast-enhanced CT, and on pathology, including immunohistochemistry. Angiographic characterization of the tumors was performed in 3 pigs. RESULTS: Pancreatic tumors developed at 19 out of 22 sites (86%) that were inoculated. Average tumor size was 3.0 cm at 1 week (range: 0.5-5.1 cm). H&E and immunohistochemical stains revealed undifferentiated carcinomas, similar to those of the pancreatobiliary system in humans. Neoplastic cells were accompanied by a major inflammatory component. 1 of 12 pigs only had inflammatory nodules without evidence of neoplasia. On multiphase CT, tumors were hypovascular compared to the normal pancreas. There was no pancreatic duct dilation. In 3 pigs, angiography was performed, and in all 3 cases, the artery supplying the pancreatic tumor could be catheterized using a 2.4 F microcatheter. Selective angiography showed the pancreatic tumor, without extra-pancreatic perfusion. CONCLUSION: Pancreatic cancer can be induced in a transgenic pig. Intra-arterial procedures using catheters designed for human interventions were technically feasible in this large animal model.
Journal Title: PLoS ONE
Volume: 15
Issue: 9
ISSN: 1932-6203
Publisher: Public Library of Science  
Date Published: 2020-09-21
Start Page: e0239391
Language: English
DOI: 10.1371/journal.pone.0239391
PUBMED: 32956389
PROVIDER: scopus
PMCID: PMC7505440
DOI/URL:
Notes: Article -- Source: Scopus
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MSK Authors
  1. Olca Basturk
    353 Basturk
  2. Stephen Solomon
    429 Solomon
  3. Sebastien Monette
    151 Monette
  4. David P Kelsen
    538 Kelsen
  5. Gokce Askan
    77 Askan
  6. Franz Edward Boas
    77 Boas
  7. Etay   Ziv
    116 Ziv
  8. Fuad Nurili
    24 Nurili
  9. Achiude Bendet
    8 Bendet
  10. Adam Oliver Michel
    19 Michel