ArticleCancer research2013
Th-MYCN mice with caspase-8 deficiency develop advanced neuroblastoma with bone marrow metastasis.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 65 citations in OpenAlex.
- Conservation of Epithelial-to-Mesenchymal Transition Process in Neural Crest Cells and Metastatic Cancer.Cells, tissues, organs · 2021Pooled it
- Immune remodeling and myeloid signature in the bone marrow niche of MYCN-driven neuroblastoma.BJC reports · 2026Article
- Oncogenic KRAS-driven type I interferon signalling primes pancreatic cancer for necroptosis.Nature communications · 2026Article
- Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development.Neuro-oncology · 2025Article
- Three-Dimensional Culture Systems in Neuroblastoma Research.Organoids · 2025Article
- Targeting SWI/SNF ATPases reduces neuroblastoma cell plasticity.The EMBO journal · 2024Article
- Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma.Frontiers of medicine · 2024Article
- RT-PCR demonstrates superior sensitivity and specificity in detecting the five neuroblastoma genes compared to the flow cytometry method for measurable residual disease.Translational pediatrics · 2023Article
- Epigenetic Dysregulation inInternational journal of molecular sciences · 2023Review
- Adaptation of the Th-MYCN Mouse Model of Neuroblastoma for Evaluation of Disseminated Disease.International journal of molecular sciences · 2023Article
- Review
- Metastasis in neuroblastoma: theFrontiers in oncology · 2023Review
- Review
- The Significance of Histopathologic Assessment in Bone Marrow Disease in Neuroblastoma.Turk patoloji dergisi · 2022Article
- MYCN in Neuroblastoma: "Old Wine into New Wineskins".Diseases (Basel, Switzerland) · 2021Review
- Review
- Hypoxia-inducible factors individually facilitate inflammatory myeloid metabolism and inefficient cardiac repair.The Journal of experimental medicine · 2021Article
- GAS7 Deficiency Promotes Metastasis in MYCN-Driven Neuroblastoma.Cancer research · 2021Article
- The role of caspase-8 in the tumor microenvironment of ovarian cancer.Cancer metastasis reviews · 2021Review
- Targeting apoptotic caspases in cancer.Biochimica et biophysica acta. Molecular cell research · 2020Review
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Neuroblastoma, the most common extracranial pediatric solid tumor, is responsible for 15% of all childhood cancer deaths. Patients frequently present at diagnosis with metastatic disease, particularly to the bone marrow. Advances in therapy and understanding of the metastatic process have been limited due, in part, to the lack of animal models harboring bone marrow disease. The widely used transgenic model, the Th-MYCN mouse, exhibits limited metastasis to this site. Here, we establish the first genetic immunocompetent mouse model for metastatic neuroblastoma with enhanced secondary tumors in the bone marrow. This model recapitulates 2 frequent alterations in metastatic neuroblastoma, overexpression of MYCN and loss of caspase-8 expression. Mouse caspase-8 gene was deleted in neural crest lineage cells by crossing a Th-Cre transgenic mouse with a caspase-8 conditional knockout mouse. This mouse was then crossed with the neuroblastoma prone Th-MYCN mouse. Although overexpression of MYCN by itself rarely caused bone marrow metastasis, combining MYCN overexpression and caspase-8 deletion significantly enhanced bone marrow metastasis (37% incidence). Microarray expression studies of the primary tumors mRNAs and microRNAs revealed extracellular matrix structural changes, increased expression of genes involved in epithelial to mesenchymal transition, inflammation, and downregulation of miR-7a and miR-29b. These molecular changes have been shown to be associated with tumor progression and activation of the cytokine TGF-β pathway in various tumor models. Cytokine TGF-β can preferentially promote single cell motility and blood-borne metastasis and therefore activation of this pathway may explain the enhanced bone marrow metastasis observed in this animal model.
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