{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["12(12)"],"submitter":["Semba T"],"funding":["Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan"],"pubmed_abstract":["Somatic mutations in <i>EGFR</i> and <i>KRAS</i> as well as chromosome rearrangements affecting <i>ALK</i>, <i>ROS1</i>, and <i>RET</i> have been identified in human lung adenocarcinoma (LUAD). We here developed organoid-based orthotopic and syngeneic mouse models for studies of the pathogenesis and treatment of LUAD. We isolated EpCAM-positive epithelial cells from mouse lungs and cultured them as organoids to maintain epithelial stem cell properties. These cells were transformed by KRAS(G12V) or EML4-ALK and then transplanted via the trachea into the lungs of the syngeneic mice, where they formed tumors that expressed the lung lineage marker TTF-1 and which closely recapitulated the pathology of human LUAD. Treatment with crizotinib suppressed the growth of tumors formed by the EML4-ALK-expressing lung epithelial cells in a subcutaneous transplantation model. Organoid culture of normal lung epithelial cells resulted in enrichment of EpCAM<sup>+</sup>SCA-1(Ly6a)<sup>+</sup> cells as well as in that of cells expressing another member of the Ly6 protein family, Ly6d, which was found to be required for the growth of the LUAD-initiating cells expressing KRAS(G12V) or EML4-ALK. We also found that a high expression level of <i>LY6D</i> was associated with poor prognosis in human LUAD. Our results thus suggest that LY6D is a potential lung cancer stem cell marker."],"journal":["Cancers"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7767274"],"repository":["biostudies-literature"],"pubmed_title":["Lung Adenocarcinoma Mouse Models Based on Orthotopic Transplantation of Syngeneic Tumor-Initiating Cells Expressing EpCAM, SCA-1, and Ly6d."],"pmcid":["PMC7767274"],"funding_grant_id":["KAKENHI 20K08968","KAKENHI 22130007"],"pubmed_authors":["Kasuga A","Semba T","Suina K","Kohno T","Sato R","Shibata T","Suzuki M","Arima Y","Saya H"],"additional_accession":[]},"is_claimable":false,"name":"Lung Adenocarcinoma Mouse Models Based on Orthotopic Transplantation of Syngeneic Tumor-Initiating Cells Expressing EpCAM, SCA-1, and Ly6d.","description":"Somatic mutations in <i>EGFR</i> and <i>KRAS</i> as well as chromosome rearrangements affecting <i>ALK</i>, <i>ROS1</i>, and <i>RET</i> have been identified in human lung adenocarcinoma (LUAD). We here developed organoid-based orthotopic and syngeneic mouse models for studies of the pathogenesis and treatment of LUAD. We isolated EpCAM-positive epithelial cells from mouse lungs and cultured them as organoids to maintain epithelial stem cell properties. These cells were transformed by KRAS(G12V) or EML4-ALK and then transplanted via the trachea into the lungs of the syngeneic mice, where they formed tumors that expressed the lung lineage marker TTF-1 and which closely recapitulated the pathology of human LUAD. Treatment with crizotinib suppressed the growth of tumors formed by the EML4-ALK-expressing lung epithelial cells in a subcutaneous transplantation model. Organoid culture of normal lung epithelial cells resulted in enrichment of EpCAM<sup>+</sup>SCA-1(Ly6a)<sup>+</sup> cells as well as in that of cells expressing another member of the Ly6 protein family, Ly6d, which was found to be required for the growth of the LUAD-initiating cells expressing KRAS(G12V) or EML4-ALK. We also found that a high expression level of <i>LY6D</i> was associated with poor prognosis in human LUAD. Our results thus suggest that LY6D is a potential lung cancer stem cell marker.","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Dec","modification":"2021-02-20T16:44:45Z","creation":"2021-02-20T16:44:45Z"},"accession":"S-EPMC7767274","cross_references":{"pubmed":["33348616"],"doi":["10.3390/cancers12123805"]}}