Induction and preliminary characterization of neoplastic pulmonary nodules in a transgenic pig model Journal Article
| Authors: | Ghosn, M.; Elsakka, A. S.; Petre, E. N.; Cheleuitte-Nieves, C.; Tammela, T.; Monette, S.; Ziv, E.; Schachtschneider, K. M.; Srimathveeravalli, G.; Yarmohammadi, H.; Boas, F. E.; Solomon, S. B. |
| Article Title: | Induction and preliminary characterization of neoplastic pulmonary nodules in a transgenic pig model |
| Abstract: | Objectives: Lung cancer models in large animals are lacking. Oncopigs are transgenic pigs that carry both KRASG12D and TP53R167H Cre-inducible mutations. This study aimed to develop and histologically characterize a swine model of lung cancer that could serve for preclinical studies evaluating locoregional therapies. Materials and Methods: In two Oncopigs, an adenoviral vector encoding the Cre-recombinase gene (AdCre) was injected endovascularly through the pulmonary arteries or inferior vena cava. In two other Oncopigs, a lung biopsy was performed and incubated with AdCre, before reinjecting the mixture into the lungs percutaneously. Animals were clinically and biologically (complete blood count, liver enzymes and lipasemia) monitored. Ob- tained tumors were characterized on computed tomography (CT) and on pathology and immunohistochemistry (IHC).Results: Neoplastic lung nodules developed following 1 (1/10, 10%) endovascular inoculation, and 2 (2/6, 33%) percutaneous inoculations. All lung tumors were visible at the 1-week CT, and appeared as well-circumscribed solid nodules, with a median longest diameter of 14 mm (range: 5-27 mm). Only one complication occurred: an extravasation of the mixture into the thoracic wall during a percutaneous injection that resulted in a thoracic wall tumor. Pigs remained clinically healthy during the entire follow-up (14-21 days). On histology, tumors consisted of inflammatory undifferentiated neoplasms composed of atypical spindle and epithelioid cells and/or a fibrovascular stroma and abundant mixed leukocytic infiltrate. On IHC, atypical cells diffusely displayed expression of vimentin and some showed expression of CK WSS and CK 8/18. The tumor microenvironment contained abundant IBA1 + macrophages and giant cells, CD3 + T cells, and CD31 + blood vessels.Conclusion: Tumors induced in the lungs of Oncopigs are fast growing poorly differentiated neoplasms associated with a marked inflammatory reaction that can be easily and safely induced at site specific locations. This large animal model might be suitable for interventional and surgical therapies of lung cancer. |
| Keywords: | lung cancer; cell transformation; metastases; tumor; swine; radiofrequency; cell lung-cancer; combination; neoplastic; origin; microwave ablation; thermal ablation; transgenic animals; viral cell transformation |
| Journal Title: | Lung Cancer |
| Volume: | 178 |
| ISSN: | 0169-5002 |
| Publisher: | Elsevier Ireland Ltd. |
| Date Published: | 2023-04-01 |
| Start Page: | 157 |
| End Page: | 165 |
| Language: | English |
| ACCESSION: | WOS:000950002300001 |
| DOI: | 10.1016/j.lungcan.2023.02.013 |
| PROVIDER: | wos |
| PUBMED: | 36868176 |
| PMCID: | PMC10538441 |
| Notes: | Article -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed and PDF -- MSK corresponding author is Stephen Solomon -- Source: Wos |
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