Development and comprehensive characterization of porcine hepatocellular carcinoma for translational liver cancer investigation.

Autor:	Gaba RC; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.; Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA., Elkhadragy L; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., Boas FE; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, USA., Chaki S; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Chen HH; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., El-Kebir M; Department of Computer Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Garcia KD; Biological Resources Laboratory, University of Illinois at Chicago, Chicago, IL, USA., Giurini EF; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., Guzman G; Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA., LoBianco FV; College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR, USA., Neto MF; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., Newson JL; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., Qazi A; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Regan M; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA., Rund LA; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Schwind RM; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA., Stewart MC; College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Thomas FM; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Whiteley HE; College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Wu J; Department of Computer Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Schook LB; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.; Department of Animal Sciences, University of Illinois at Urbana-Champaign, Urbana, IL, USA.; National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA., Schachtschneider KM; Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.; Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, Chicago, IL, USA.; National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Jazyk:	angličtina
Zdroj:	Oncotarget [Oncotarget] 2020 Jul 14; Vol. 11 (28), pp. 2686-2701. Date of Electronic Publication: 2020 Jul 14 (Print Publication: 2020).
DOI:	10.18632/oncotarget.27647
Abstrakt:	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. Competing Interests: CONFLICTS OF INTEREST Ron C. Gaba receives research support from Guerbet USA LLC, Janssen Research & Development LLC, the United States Department of Defense, and the United States National Institutes of Health. F. Edward Boas is a co-founder of Claripacs, LLC. He received research funding (investigator-initiated) from Guerbet. He received research support (investigator-initiated) from GE. He received research supplies (investigator-initiated) from Bayer. He received a research grant and speaker fees from Society of Interventional Oncology, which were sponsored by Guerbet. He attended research meetings sponsored by Guerbet. He is an investor in Labdoor, Qventus, CloudMedx, Notable Labs, and Xgenomes. He is the inventor and assignee on US patent 8233586, and is an inventor on US provisional patent applications 62/754,139 and 62/817,116. Regina M. Schwind receives research support from Guerbet USA LLC and Janssen Research & Development LLC. Lawrence B. Schook research support from Guerbet USA LLC, Janssen Research & Development LLC, the United States Department of Defense, and the United States National Institutes of Health. Kyle M. Schachtschneider receives research support from Guerbet USA LLC, Janssen Research & Development LLC, and the United States National Institutes of Health. The remaining authors—Lobna Elkhadragy, Sulalita Chaki, Hanna H. Chen, Mohammed El-Kebir, Kelly D. Garcia, Eileena F. Giurini, Grace Guzman, Francesca V. LoBianco, Mario F. Neto, Jordan L. Newson, Aisha Qazi, Maureen Regan, Lauretta A. Rund, Matthew C. Stewart, Faith M. Thomas, Herbert E. Whiteley, and Jiaqi Wu—have no reported conflicts of interest.
Databáze:	MEDLINE
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