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Angptl-7 knockdown RNA sequencing of 4T1 orthotopic transplants into rat mammary fat pads

ABSTRACT: These samples are derived from tissues obtained from 4T1 spheroids transplanted orthotopically into the mammary fat pads of SRG OncoRats. 4T1 cell lines were established by viral transduction that stably express either a non-targeting control shRNA (NT4) or an shRNA targeting Angptl-7. 4T1 cells were cultured as spheroids in suspension for 24-hours prior to transplantation in 2% matrigel. 600,000 cells in a 1:1 mixture of matrigel and DMEM/F12 were transplanted orthotopically into the right T4 fat pads of SRG rats. At day 27 post transplanation, primary tumors. The primary tumors were cut in half to expose the cross-section, and the tumors were dissected to isolate the necrotic core region and the non-necrotic rim region. Samples were snap frozen and sent to Genewiz-Azenta for RNA extraction, library prep, and next-gen sequencing.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE224232 | GEO | 2024/01/01

REPOSITORIES: GEO

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Project description:Novel therapies targeting cancer stem cells (CSCs), which play critical roles in chemo- and radio-resistance, metastasis, and possibly resistance against cancer immunotherapy including granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines, may provide beneficial clinical outcomes. Here, we used syngeneic immunocompetent mice that allowed precise evaluation of the immunogenicity of the side population (SP) isolated from 4T1 murine breast carcinoma (4T1-SP) cells as putative CSCs. 4T1-SP cells showed various stem cell properties including high capacities for colony formation and tumorigenicity as well as high expression of phosphorylated signal transducer and activator of transcription-3 and vascular endothelial growth factor that are inductive of immune tolerance. Despite these progressive malignant characteristics of 4T1-SP cells, subcutaneous injection of non-transmissible Sendai virus-mediated GM-CSF gene-transduced 4T1-SP (4T1-SP/GM) cells remarkably impaired their tumorigenicity compared with that of the controls. This impairment of tumorigenicity was partially dependent on CD8+ T cells in concert with CD4+ T cells and natural killer cells. Notably, therapeutic vaccinations using irradiated 4T1-SP/GM cells markedly suppressed tumor development of subcutaneously transplanted 4T1-SP cells compared with that of the controls including irradiated 4T1-non-SP/GM cells. Tumor suppression was accompanied by robust accumulation of mature dendritic cells at vaccination sites and systemic Th1-based cellular immunity. Moreover, vaccinations comprising primary 4T1-SP cells isolated from transplanted 4T1-SP tumors elicited antitumor effects. cDNA microarray analysis showed that 4T1-SP cells predominantly expressed genes of cancer-related antigens including cancer/testis antigens. Collectively, we demonstrate that SP cell-based vaccinations induce effective antitumor immunity that may improve the efficacy of SP cell-based immunotherapy. Gene expression profiles were compared between sorted 4T1-SP and 4T1-NSP cells.

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Angptl-7 knockdown RNA sequencing of 4T1 orthotopic transplants into rat mammary fat pads

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