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

• DOI: 10.18632/oncotarget.27647
• Publication Date: 2020-07-14T15:16:08Z
• Authors: Ron C. Gaba; Lobna Elkhadragy; F. Edward Boas; Sulalita Chaki; Hanna H. Chen; Mohammed El-Kebir; Kelly D. Garcia; Eileena F. Giurini; Grace Guzman; Francesca V. LoBi...; Mario F. Neto; Jordan L. Newson; Aisha Qazi; Maureen Regan; Lauretta A. Rund; Regina M. Schwind; Matthew C. Stewart; Faith M. Thomas; Herbert E. Whiteley; Jiaqi Wu; Lawrence B. Schook; Kyle M. Schachtsc...
• Keywords: 0303 health sciences; 03 medical and health sciences; Research Paper; 3. Good health

// Ron C. Gaba 1 , 2 Lobna Elkhadragy F. Edward Boas 3 Sulalita Chaki 4 Hanna H. Chen Mohammed El-Kebir 5 Kelly D. Garcia 6 Eileena Giurini Grace Guzman Francesca V. LoBianco 7 Mario Neto Jordan L. Newson Aisha Qazi Maureen Regan 8 Lauretta A. Rund Regina M. Schwind Matthew Stewart 9 Faith Thomas Herbert E. Whiteley Jiaqi Wu Lawrence B. Schook 10 and Kyle Schachtschneider Department of Radiology, University Illinois at Chicago, IL, USA Pathology, Memorial Sloan Kettering Cancer Center, New York City, NY, Animal Sciences, Urbana-Champaign, Urbana, Computer Biological Resources Laboratory, College Medicine, Arkansas for Medical Little Rock, AR, Biochemistry Molecular Genetics, Veterinary National Center Supercomputing Applications, Correspondence to: Schachtschneider, email: [e-mail] Keywords: liver cancer; transgenic pigs; large animal model; interventional radiology; personalized medicine Received: April 13, 2020 Accepted: June 01, Published: July 14, ABSTRACT Hepatocellular carcinoma (HCC) is the second leading cause cancer-related death worldwide. models that faithfully recapitulate human HCC phenotypes are required to address unmet clinical needs advance standard-of-care therapeutics. This study utilized Oncopig Model develop a translational porcine model which can serve as bridge between murine studies practice. Reliable development cell lines was demonstrated through hepatocyte isolation Cre recombinase exposure across 15 Oncopigs. displayed similar cycle lengths, alpha-fetoprotein production, arginase-1 staining, chemosusceptibility, drug metabolizing enzyme expression. The ability cells consistently produce tumors in vivo confirmed via subcutaneous (SQ) injection into immunodeficient mice Reproducible intrahepatic an alcohol-induced fibrotic microenvironment achieved engraftment SQ livers. Whole-genome sequencing demontrated tumor tissue resembled genomic level. Finally, amenable gene editing tumors. provides novel, clinically-relevant holds great promise improving outcomes testing novel therapeutic approaches accelerate enhance trials.