{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lahdeniemi IAK"],"funding":["Terveyden Tutkimuksen Toimikunta","Institute for Molecular Medicine Finland: Helsingin yliopisto Suomen molekyylilaaketieteen instituutti","Core"],"pagination":["bio059623"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9770245"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["11(12)"],"pubmed_abstract":["Preclinical tumor models with native tissue microenvironments provide essential tools to understand how heterogeneous tumor phenotypes relate to drug response. Here we present syngeneic graft models of aggressive, metastasis-prone histopathology-specific NSCLC tumor types driven by KRAS mutation and loss of LKB1 (KL): adenosquamous carcinoma (ASC) and adenocarcinoma (AC). We show that subcutaneous injection of primary KL; ASC cells results in squamous cell carcinoma (SCC) tumors with high levels of stromal infiltrates, lacking the source heterogeneous histotype. Despite forming subcutaneous tumors, intravenously injected KL;AC cells were unable to form lung tumors. In contrast, intravenous injection of KL;ASC cells leads to their lung re-colonization and lesions recapitulating the mixed AC and SCC histopathology, tumor immune suppressive microenvironment and oncogenic signaling profile of source tumors, demonstrating histopathology-selective phenotypic dominance over genetic drivers. Pan-ERBB inhibition increased survival, while selective ERBB1/EGFR inhibition did not, suggesting a role of the ERBB network crosstalk in resistance to ERBB1/EGFR. This immunocompetent NSCLC lung colonization model hence phenocopies key properties of the metastasis-prone ASC histopathology, and serves as a preclinical model to dissect therapy responses and metastasis-associated processes."],"journal":["Biology open"],"pubmed_title":["Development of an adenosquamous carcinoma histopathology - selective lung metastasis model."],"pmcid":["PMC9770245"],"funding_grant_id":["307111"],"pubmed_authors":["Nagaraj AS","Lahdeniemi IAK","Verschuren EW","Devlin JR","Talwelkar SS","Bao J","Hemmes A","Seref Vujaklija C","Kiss EA","Linnavirta N"],"additional_accession":[]},"is_claimable":false,"name":"Development of an adenosquamous carcinoma histopathology - selective lung metastasis model.","description":"Preclinical tumor models with native tissue microenvironments provide essential tools to understand how heterogeneous tumor phenotypes relate to drug response. Here we present syngeneic graft models of aggressive, metastasis-prone histopathology-specific NSCLC tumor types driven by KRAS mutation and loss of LKB1 (KL): adenosquamous carcinoma (ASC) and adenocarcinoma (AC). We show that subcutaneous injection of primary KL; ASC cells results in squamous cell carcinoma (SCC) tumors with high levels of stromal infiltrates, lacking the source heterogeneous histotype. Despite forming subcutaneous tumors, intravenously injected KL;AC cells were unable to form lung tumors. In contrast, intravenous injection of KL;ASC cells leads to their lung re-colonization and lesions recapitulating the mixed AC and SCC histopathology, tumor immune suppressive microenvironment and oncogenic signaling profile of source tumors, demonstrating histopathology-selective phenotypic dominance over genetic drivers. Pan-ERBB inhibition increased survival, while selective ERBB1/EGFR inhibition did not, suggesting a role of the ERBB network crosstalk in resistance to ERBB1/EGFR. This immunocompetent NSCLC lung colonization model hence phenocopies key properties of the metastasis-prone ASC histopathology, and serves as a preclinical model to dissect therapy responses and metastasis-associated processes.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2024-11-19T17:54:08.93Z","creation":"2024-11-19T17:54:08.93Z"},"accession":"S-EPMC9770245","cross_references":{"pubmed":["36355420"],"doi":["10.1242/bio.059623"]}}