Generation of Novel Immunocompetent Mouse Cell Lines to Model Experimental Metastasis of High-Risk Neuroblastoma
Year: 2023
Type: article
Abstract: NB, being a highly metastatic cancer, is one of the leading causes of cancer-related deaths in children. Increased disease recurrence and clinical resistance in patients with metastatic high-risk NBs (HR-NBs) result in poor outcomes and lower overall survival. However, the paucity of appropriate in vivo models for HR-NB metastasis has limited investigations into the underlying biology of HR-NB metastasis. This study was designed to address this limitation and develop suitable immunocompetent models for HR-NB metastasis. Here, we developed several highly metastatic immunocompetent murine HR-NB cell lines. Our newly developed cell lines show 100% efficiency in modeling experimental metastasis in C57BL6 mice and feature metastasis to the sites frequently observed in humans with HR-NB (liver and bone). In vivo validation demonstrated their specifically gained metastatic phenotype. The in vitro characterization of the cell lines showed increased cell invasion, acquired anchorage-independent growth ability, and resistance to MHC-I induction upon IFN-γ treatment. Furthermore, RNA-seq analysis of the newly developed cells identified a differentially regulated gene signature and an enrichment of processes consistent with their acquired metastatic phenotype, including extracellular matrix remodeling, angiogenesis, cell migration, and chemotaxis. The presented newly developed cell lines are, thus, suitable and promising tools for HR-NB metastasis and microenvironment studies in an immunocompetent system.
Source: Cancers
Authors: Mayura R. Dhamdhere, Dan V. Spiegelman, Lisa Schneper, Amy K. Erbe, Paul M. Sondel, Vladimir S. Spiegelman
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,892
Funders: Alex's Lemonade Stand Foundation for Childhood Cancer, University of Pennsylvania, University of Wisconsin Carbone Cancer Center, Pennsylvania State University, Midwest Athletes Against Childhood Cancer, Four Diamonds, Cancer Research UK, National Institutes of Health, Penn State College of Medicine, National Cancer Institute, National Institute of Dental and Craniofacial Research
Awards: G1020178090, G1359571829, G1420127368, G1475746525, G1485999944, G181383032, G1930467333, G2774106916, G3047783705, G3398397080, G3746373416, Head and Neck Cancer SPORE at the University of Wisconsin, G4722363824, G4725453866, G5334511249, G5440856869, G5449838093, G5483775087, G62584183, G6546753649, G6656429489, G7293660262, G7658213480, G8331991649, G8875153088, G9000040766, G9000052052, G9000071658, G9000189851
OpenAlex ID: W4386996019