RRC ID |
52526
|
著者 |
Woodfield SE, Shi Y, Patel RH, Jin J, Major A, Sarabia SF, Starosolski Z, Zorman B, Gupta SS, Chen Z, Ibarra AM, Bissig KD, Ghaghada KB, Sumazin P, López-Terrada D, Vasudevan SA.
|
タイトル |
A Novel Cell Line Based Orthotopic Xenograft Mouse Model That Recapitulates Human Hepatoblastoma.
|
ジャーナル |
Sci Rep
|
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.
|
巻・号 |
7(1)
|
ページ |
17751
|
公開日 |
2017-12-19
|
DOI |
10.1038/s41598-017-17665-8
|
PII |
10.1038/s41598-017-17665-8
|
PMID |
29259231
|
PMC |
PMC5736579
|
MeSH |
Animals
Carcinoma, Hepatocellular* / blood supply
Carcinoma, Hepatocellular* / diagnostic imaging
Carcinoma, Hepatocellular* / metabolism
Carcinoma, Hepatocellular* / pathology
Hep G2 Cells
Heterografts
Humans
Liver Neoplasms, Experimental* / blood supply
Liver Neoplasms, Experimental* / diagnostic imaging
Liver Neoplasms, Experimental* / metabolism
Liver Neoplasms, Experimental* / pathology
Mice
Mice, Inbred NOD
Mice, SCID
Neoplasm Transplantation*
Neovascularization, Pathologic* / diagnostic imaging
Neovascularization, Pathologic* / metabolism
Neovascularization, Pathologic* / pathology
Xenograft Model Antitumor Assays
|
IF |
3.998
|
引用数 |
7
|
リソース情報 |
ヒト・動物細胞 |
HuH-6(RCB1367) |