Open AccessHepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells
Author(s) -
Sarah E. Woodfield,
Brandon Mistretta,
Roma H. Patel,
Aryana M. Ibarra,
Kevin E. Fisher,
Stephen F. Sarabia,
Ilavarasi Gandhi,
Jacquelyn Reuther,
Zbigniew Starosolski,
Andrew Badachhape,
Jessica Epps,
Barry Zorman,
Aayushi Shah,
Samuel R. Larson,
Rohit Srivastava,
Yan Shi,
Andres F. Espinoza,
Saiabhiroop R Govindu,
Richard S. Whitlock,
Kimberly Holloway,
Angshumoy Roy,
Pavel Sumazin,
Ketan B. Ghaghada,
Dolores LópezTerrada,
Preethi H. Gunaratne,
Sanjeev A. Vasudevan
Publication year - 2022
Publication title -
biology open
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.936
H-Index - 41
ISSN - 2046-6390
DOI - 10.1242/bio.058973
Subject(s) - hepatoblastoma , biology , metastasis , cancer research , tumor cells , circulating tumor cell , medicine , cancer , genetics
Hepatoblastoma (HB) is the most common pediatric primary liver malignancy, and survival for high-risk disease approaches 50%. Mouse models of HB fail to recapitulate hallmarks of high-risk disease. The aim of this work was to generate murine models that show high-risk features including multifocal tumors, vascular invasion, metastasis, and circulating tumor cells (CTCs). HepT1 cells were injected into the livers or tail veins of mice, and tumor growth was monitored with magnetic resonance and bioluminescent imaging. Blood was analyzed with fluorescence activated cell sorting to identify CTCs. Intra- and extra-hepatic tumor samples were harvested for immunohistochemistry and RNA and DNA sequencing. Cell lines were grown from tumor samples and profiled with RNA sequencing. With intrahepatic injection of HepT1 cells, 100% of animals grew liver tumors and showed vascular invasion, metastasis, and CTCs. Mutation profiling revealed genetic alterations in seven cancer-related genes, while transcriptomic analyses showed changes in gene expression with cells that invade vessels. Tail vein injection of HepT1 cells resulted in multifocal, metastatic disease. These unique models will facilitate further meaningful studies of high-risk HB.