{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T04:21:02Z","timestamp":1772252462987,"version":"3.50.1"},"reference-count":96,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,14]],"date-time":"2025-09-14T00:00:00Z","timestamp":1757808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Rally Foundation","award":["22IN42"],"award-info":[{"award-number":["22IN42"]}]},{"name":"Rally Foundation","award":["1419786"],"award-info":[{"award-number":["1419786"]}]},{"name":"Rally Foundation","award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}]},{"name":"Alex\u2019s Lemonade Stand Foundation","award":["22IN42"],"award-info":[{"award-number":["22IN42"]}]},{"name":"Alex\u2019s Lemonade Stand Foundation","award":["1419786"],"award-info":[{"award-number":["1419786"]}]},{"name":"Alex\u2019s Lemonade Stand Foundation","award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}]},{"name":"University of Pittsburgh Center for Research Computing","award":["22IN42"],"award-info":[{"award-number":["22IN42"]}]},{"name":"University of Pittsburgh Center for Research Computing","award":["1419786"],"award-info":[{"award-number":["1419786"]}]},{"name":"University of Pittsburgh Center for Research Computing","award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}]},{"name":"NIH","award":["22IN42"],"award-info":[{"award-number":["22IN42"]}]},{"name":"NIH","award":["1419786"],"award-info":[{"award-number":["1419786"]}]},{"name":"NIH","award":["S10OD028483"],"award-info":[{"award-number":["S10OD028483"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Hepatoblastoma (HB), the most common pediatric liver cancer, often bears mutations in and\/or otherwise deregulates the oncogenic transcription factors \u03b2-catenin (B), YAP (Y) and NRF2 (N). HB research is hampered by a paucity of established cell lines, particularly those possessing these molecular drivers. All combinations of B, Y and N (BY, BN, YN and BYN) are tumorigenic when overexpressed in murine livers, but it has not been possible to establish cell lines from primary tumors. Recently, we found that concurrent, in vivo Crispr-mediated targeting of the Cdkn2a tumor suppressor locus allows for immortalized cell lines to be efficiently generated. Methods: We derived and characterized five immortalized cell lines from Cdkn2a-targeted BN and YN HBs. Results: Four of the above five cell lines retained their ability to grow as subcutaneous or \u201cpseudo-metastatic\u201d pulmonary tumors in the immunocompetent mice from which they originated. Most notably, when maintained under hypoxic conditions for as little as 2 days, BN cells transiently upregulated the expression of numerous endothelial cell (EC)-specific genes and acquired EC-like properties that benefited tumor growth. These lines and those from previously derived BY and BYN HBs also possessed similar sensitivities to four commonly employed chemotherapeutic drugs. Conclusions: The above-described approach is currently the only means to generate HB cell lines with pre-selected and clinically relevant oncogenic drivers. Its generic nature should also allow bespoke HB cell lines with other oncogenic drivers to be readily produced. A collection of such cell lines will be useful for studying tumor cell-to-EC trans-differentiation, interactions with the immune environment and drug sensitivities.<\/jats:p>","DOI":"10.3390\/cancers17183002","type":"journal-article","created":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T09:43:41Z","timestamp":1757929421000},"page":"3002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Derivation of Genetically Defined Murine Hepatoblastoma Cell Lines with Angiogenic Potential"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8300-8288","authenticated-orcid":false,"given":"Keyao","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"School of Medicine, Tsinghua Medicine, Tsinghua University, Beijing 100084, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1479-6489","authenticated-orcid":false,"given":"Ahmet","family":"Toksoz","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"Kanuni Sultan Suleiman Training and Research Hospital, Istanbul 34303, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Henchy","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"The University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Knapp","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"The University of Pittsburgh, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Lu","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6214-9167","authenticated-orcid":false,"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2551-3243","authenticated-orcid":false,"given":"Huabo","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9666-8205","authenticated-orcid":false,"given":"Edward V.","family":"Prochownik","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, UPMC Children\u2019s Hospital of Pittsburgh, Pittsburgh, PA 15224, USA"},{"name":"The Department of Microbiology and Molecular Genetics, The University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA"},{"name":"The UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA"},{"name":"The University of Pittsburgh Liver Research Center, Pittsburgh, PA 15213, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e30505","DOI":"10.1002\/pbc.30505","article-title":"Consensus Classification of Pediatric Hepatocellular Tumors: A Report from the Children\u2019s Hepatic Tumors International Collaboration (Chic)","volume":"70","author":"Cho","year":"2023","journal-title":"Pediatr. 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