TY - JOUR
T1 - A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
AU - Woodfield, Sarah E.
AU - Shi, Yan
AU - Patel, Roma H.
AU - Jin, Jingling
AU - Major, Angela
AU - Sarabia, Stephen F.
AU - Starosolski, Zbigniew
AU - Zorman, Barry
AU - Gupta, Siddharth S.
AU - Chen, Zhenghu
AU - Ibarra, Aryana M.
AU - Bissig, Karl Dimiter
AU - Ghaghada, Ketan B.
AU - Sumazin, Pavel
AU - López-Terrada, Dolores
AU - Vasudevan, Sanjeev A.
N1 - Funding Information:
We would like to thank Saakshi Bhayana and Dr. Igor Stupin for assistance with MRI. We would like to thank Pamela Parsons in the Texas Medical Center Digestive Diseases Center for completing the immunohistochemistry experiments with our samples. S.A.V. is supported by a Texas Children’s Department of Surgery Seed Award and the Macy Easom Cancer Research Foundation. K.D.B. is supported by the National Heart, Lung, and Blood Institute (NHLBI) grant R01HL134510, the Texas Hepatocellular Carcinoma Consortium (THCC) CPRIT grant RP150587, and the Diane Helis Henry and Adrienne Helis Malvin Medical Research Foundation. The Baylor College of Medicine Dan L. Duncan Cancer Center is supported by NIH grant P30CA125123. The Texas Medical Center Digestive Diseases Center is supported by NIH grant P30DK56338.
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human α-fetoprotein (AFP) were monitored in the serum of animals. Immunohistochemical and gene expression analyses were also completed on xenograft tumor samples. BLI signal indicative of tumor growth was seen in 55% of HepG2- and Huh-6-injected animals after a period of four to seven weeks. Increased AFP levels correlated with tumor growth. MRI showed large intrahepatic tumors with active neovascularization. HepG2 and Huh-6 xenografts showed expression of β-catenin, AFP, and Glypican-3 (GPC3). HepG2 samples displayed a consistent gene expression profile most similar to human HB tumors. Intrahepatic injection of HB cell lines leads to liver tumors in mice with growth patterns and biologic, histologic, and genetic features similar to human HB tumors. This orthotopic xenograft mouse model will enable clinically relevant testing of novel agents for HB.
AB - Currently, preclinical testing of therapies for hepatoblastoma (HB) is limited to subcutaneous and intrasplenic xenograft models that do not recapitulate the hepatic tumors seen in patients. We hypothesized that injection of HB cell lines into the livers of mice would result in liver tumors that resemble their clinical counterparts. HepG2 and Huh-6 HB cell lines were injected, and tumor growth was monitored with bioluminescence imaging (BLI) and magnetic resonance imaging (MRI). Levels of human α-fetoprotein (AFP) were monitored in the serum of animals. Immunohistochemical and gene expression analyses were also completed on xenograft tumor samples. BLI signal indicative of tumor growth was seen in 55% of HepG2- and Huh-6-injected animals after a period of four to seven weeks. Increased AFP levels correlated with tumor growth. MRI showed large intrahepatic tumors with active neovascularization. HepG2 and Huh-6 xenografts showed expression of β-catenin, AFP, and Glypican-3 (GPC3). HepG2 samples displayed a consistent gene expression profile most similar to human HB tumors. Intrahepatic injection of HB cell lines leads to liver tumors in mice with growth patterns and biologic, histologic, and genetic features similar to human HB tumors. This orthotopic xenograft mouse model will enable clinically relevant testing of novel agents for HB.
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U2 - 10.1038/s41598-017-17665-8
DO - 10.1038/s41598-017-17665-8
M3 - Article
C2 - 29259231
AN - SCOPUS:85038627920
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 17751
ER -