Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation Journal Article
| Authors: | Gaba, R. C.; Elkhadragy, L.; Boas, F. E.; Chaki, S.; Chen, H. H.; El-Kebir, M.; Garcia, K. D.; Giurini, E. F.; Guzman, G.; LoBianco, F. V.; Neto, M. F.; Newson, J. L.; Qazi, A.; Regan, M.; Rund, L. A.; Schwind, R. M.; Stewart, M. C.; Thomas, F. M.; Whiteley, H. E.; Wu, J.; Schook, L. B.; Schachtschneider, K. M. |
| Article Title: | Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation |
| Abstract: | Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide. New animal models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs and advance standard-of-care therapeutics. This study utilized the Oncopig Cancer Model to develop a translational porcine HCC model which can serve as a bridge between murine studies and human clinical practice. Reliable development of Oncopig HCC cell lines was demonstrated through hepatocyte isolation and Cre recombinase exposure across 15 Oncopigs. Oncopig and human HCC cell lines displayed similar cell cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, and drug metabolizing enzyme expression. The ability of Oncopig HCC cells to consistently produce tumors in vivo was confirmed via subcutaneous (SQ) injection into immunodeficient mice and Oncopigs. Reproducible development of intrahepatic tumors in an alcohol-induced fibrotic microenvironment was achieved via engraftment of SQ tumors into fibrotic Oncopig livers. Whole-genome sequencing demontrated intrahepatic tumor tissue resembled human HCC at the genomic level. Finally, Oncopig HCC cells are amenable to gene editing for development of personalized HCC tumors. This study provides a novel, clinically-relevant porcine HCC model which holds great promise for improving HCC outcomes through testing of novel therapeutic approaches to accelerate and enhance clinical trials. © Gaba et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | immunohistochemistry; protein expression; gene mutation; human cell; sorafenib; cisplatin; doxorubicin; fluorouracil; glucuronosyltransferase 1a1; liver cell carcinoma; nonhuman; comparative study; cancer grading; dna synthesis; clinical practice; biological marker; mouse; phenotype; animal tissue; cell survival; reverse transcription polymerase chain reaction; computer assisted tomography; gene expression; animal experiment; animal model; in vitro study; protein p53; histology; cancer mortality; carcinogenesis; cell heterogeneity; cell culture; cell isolation; collagen; interventional radiology; cell migration; liver cancer; liver cell; tumor growth; mitomycin; dna extraction; scid mouse; genomic dna; complementary dna; alpha fetoprotein; personalized medicine; tumor microenvironment; multidrug resistance protein 1; cytochrome p450 3a4; arginase 1; human; female; article; whole genome sequencing; organic cation transporter 1; ic50; drug metabolizing enzyme; oncogenomics; crispr-cas9 system; hep-g2 cell line; large animal model; transgenic pigs; snu-387 cell line; snu-475 cell line |
| Journal Title: | Oncotarget |
| Volume: | 11 |
| Issue: | 28 |
| ISSN: | 1949-2553 |
| Publisher: | Impact Journals |
| Date Published: | 2020-07-14 |
| Start Page: | 2686 |
| End Page: | 2701 |
| Language: | English |
| DOI: | 10.18632/oncotarget.27647 |
| PROVIDER: | scopus |
| PMCID: | PMC7367657 |
| PUBMED: | 32733642 |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
