HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells
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 t...
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| Format: | Article |
| Language: | English |
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The Company of Biologists
2022-09-01
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| Series: | Biology Open |
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| Online Access: | http://bio.biologists.org/content/11/9/bio058973 |
| _version_ | 1798020784841555968 |
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| author | Sarah E. Woodfield Brandon J. 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 P. Shah Samuel R. Larson Rohit K. Srivastava Yan Shi Andres F. Espinoza Saiabhiroop R. Govindu Richard S. Whitlock Kimberly Holloway Angshumoy Roy Pavel Sumazin Ketan B. Ghaghada Dolores Lopez-Terrada Preethi H. Gunaratne Sanjeev A. Vasudevan |
| author_facet | Sarah E. Woodfield Brandon J. 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 P. Shah Samuel R. Larson Rohit K. Srivastava Yan Shi Andres F. Espinoza Saiabhiroop R. Govindu Richard S. Whitlock Kimberly Holloway Angshumoy Roy Pavel Sumazin Ketan B. Ghaghada Dolores Lopez-Terrada Preethi H. Gunaratne Sanjeev A. Vasudevan |
| author_sort | Sarah E. Woodfield |
| collection | DOAJ |
| description | 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. This article has an associated First Person interview with the first author of the paper. |
| first_indexed | 2024-04-11T17:03:21Z |
| format | Article |
| id | doaj.art-19d25bfd932e459dbc19467d36d3ca80 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-04-11T17:03:21Z |
| publishDate | 2022-09-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-19d25bfd932e459dbc19467d36d3ca802022-12-22T04:13:06ZengThe Company of BiologistsBiology Open2046-63902022-09-0111910.1242/bio.058973058973HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cellsSarah E. Woodfield0Brandon J. Mistretta1Roma H. Patel2Aryana M. Ibarra3Kevin E. Fisher4Stephen F. Sarabia5Ilavarasi Gandhi6Jacquelyn Reuther7Zbigniew Starosolski8Andrew Badachhape9Jessica Epps10Barry Zorman11Aayushi P. Shah12Samuel R. Larson13Rohit K. Srivastava14Yan Shi15Andres F. Espinoza16Saiabhiroop R. Govindu17Richard S. Whitlock18Kimberly Holloway19Angshumoy Roy20Pavel Sumazin21Ketan B. Ghaghada22Dolores Lopez-Terrada23Preethi H. Gunaratne24Sanjeev A. Vasudevan25 Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Singleton Department of Radiology, Texas Children's Hospital, Houston, TX 77030, USA Singleton Department of Radiology, Texas Children's Hospital, Houston, TX 77030, USA Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Department of Pediatrics, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA Singleton Department of Radiology, Texas Children's Hospital, Houston, TX 77030, USA Department of Pathology and Immunology, Baylor College of Medicine, Texas Children's Hospital Department of Pathology, Houston, TX 77030, USA Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA Divisions of Pediatric Surgery and Surgical Research, Michael E. DeBakey Department of Surgery, Pediatric Surgical Oncology Laboratory, Texas Children's Surgical Oncology Program, Texas Children's Liver Tumor Program, Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA 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. This article has an associated First Person interview with the first author of the paper.http://bio.biologists.org/content/11/9/bio058973hepatoblastomapediatric liver cancermouse modelinvasionmetastasiscirculating tumor cell |
| spellingShingle | Sarah E. Woodfield Brandon J. 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 P. Shah Samuel R. Larson Rohit K. Srivastava Yan Shi Andres F. Espinoza Saiabhiroop R. Govindu Richard S. Whitlock Kimberly Holloway Angshumoy Roy Pavel Sumazin Ketan B. Ghaghada Dolores Lopez-Terrada Preethi H. Gunaratne Sanjeev A. Vasudevan HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells Biology Open hepatoblastoma pediatric liver cancer mouse model invasion metastasis circulating tumor cell |
| title | HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells |
| title_full | HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells |
| title_fullStr | HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells |
| title_full_unstemmed | HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells |
| title_short | HepT1-derived murine models of high-risk hepatoblastoma display vascular invasion, metastasis, and circulating tumor cells |
| title_sort | hept1 derived murine models of high risk hepatoblastoma display vascular invasion metastasis and circulating tumor cells |
| topic | hepatoblastoma pediatric liver cancer mouse model invasion metastasis circulating tumor cell |
| url | http://bio.biologists.org/content/11/9/bio058973 |
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