A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma

Abstract 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...

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Autores principales:	Sarah E. Woodfield, Yan Shi, Roma H. Patel, Jingling Jin, Angela Major, Stephen F. Sarabia, Zbigniew Starosolski, Barry Zorman, Siddharth S. Gupta, Zhenghu Chen, Aryana M. Ibarra, Karl-Dimiter Bissig, Ketan B. Ghaghada, Pavel Sumazin, Dolores López-Terrada, Sanjeev A. Vasudevan
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6656677b34c24573aea30e99a87fadd7
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spelling	oai:doaj.org-article:6656677b34c24573aea30e99a87fadd72021-12-02T15:05:53ZA Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma10.1038/s41598-017-17665-82045-2322https://doaj.org/article/6656677b34c24573aea30e99a87fadd72017-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-17665-8https://doaj.org/toc/2045-2322Abstract 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.Sarah E. WoodfieldYan ShiRoma H. PatelJingling JinAngela MajorStephen F. SarabiaZbigniew StarosolskiBarry ZormanSiddharth S. GuptaZhenghu ChenAryana M. IbarraKarl-Dimiter BissigKetan B. GhaghadaPavel SumazinDolores López-TerradaSanjeev A. VasudevanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sarah E. Woodfield Yan Shi Roma H. Patel Jingling Jin Angela Major Stephen F. Sarabia Zbigniew Starosolski Barry Zorman Siddharth S. Gupta Zhenghu Chen Aryana M. Ibarra Karl-Dimiter Bissig Ketan B. Ghaghada Pavel Sumazin Dolores López-Terrada Sanjeev A. Vasudevan A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
description	Abstract 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.
format	article
author	Sarah E. Woodfield Yan Shi Roma H. Patel Jingling Jin Angela Major Stephen F. Sarabia Zbigniew Starosolski Barry Zorman Siddharth S. Gupta Zhenghu Chen Aryana M. Ibarra Karl-Dimiter Bissig Ketan B. Ghaghada Pavel Sumazin Dolores López-Terrada Sanjeev A. Vasudevan
author_facet	Sarah E. Woodfield Yan Shi Roma H. Patel Jingling Jin Angela Major Stephen F. Sarabia Zbigniew Starosolski Barry Zorman Siddharth S. Gupta Zhenghu Chen Aryana M. Ibarra Karl-Dimiter Bissig Ketan B. Ghaghada Pavel Sumazin Dolores López-Terrada Sanjeev A. Vasudevan
author_sort	Sarah E. Woodfield
title	A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
title_short	A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
title_full	A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
title_fullStr	A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
title_full_unstemmed	A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma
title_sort	novel cell line based orthotopic xenograft mouse model that recapitulates human hepatoblastoma
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/6656677b34c24573aea30e99a87fadd7
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A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma

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