{"doi":"10.3390/cancers17183002","title":"Derivation of Genetically Defined Murine Hepatoblastoma Cell Lines with Angiogenic Potential","abstract":"Background/Objectives: Hepatoblastoma (HB), the most common pediatric liver cancer, often bears mutations in and/or otherwise deregulates the oncogenic transcription factors β-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 “pseudo-metastatic” 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.","journal":"Cancers","year":2025,"id":546895,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9479,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1439370,"name":"Ahmet Toksoz","orcid":null,"position":1,"is_corresponding":false},{"id":1438938,"name":"Colin Henchy","orcid":"0009-0007-8934-3104","position":2,"is_corresponding":false},{"id":1412220,"name":"Jessica Knapp","orcid":null,"position":3,"is_corresponding":false},{"id":434145,"name":"Jie Lu","orcid":"0000-0002-6982-2294","position":4,"is_corresponding":false},{"id":488800,"name":"Sarangarajan Ranganathan","orcid":"0000-0001-6214-9167","position":5,"is_corresponding":false},{"id":563216,"name":"Huabo Wang","orcid":"0000-0003-2551-3243","position":6,"is_corresponding":false},{"id":453526,"name":"Edward V. Prochownik","orcid":"0000-0001-9666-8205","position":7,"is_corresponding":false},{"id":1439369,"name":"Keyao Chen","orcid":null,"position":0,"is_corresponding":true}],"reference_count":94,"raw_metadata":null,"created_at":"2026-07-19T02:53:36.567932Z","pmid":"41008846","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}