ArticleProceedings of the National Academy of Sciences of the United States of America2013
Transient treatment with epigenetic modifiers yields stable neuroblastoma stem cells resembling aggressive large-cell neuroblastomas.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Mutually exclusive teams-like patterns of gene regulation characterize phenotypic heterogeneity along the noradrenergic-mesenchymal axis in neuroblastoma.Cancer biology & therapy · 2024Article
- Targeting the epigenome of cancer stem cells in pediatric nervous system tumors.Molecular and cellular biochemistry · 2023Review
- Neural crest-related NXPH1/α-NRXN signaling opposes neuroblastoma malignancy by inhibiting organotropic metastasis.Oncogene · 2023Article
- Evaluating the RIST Molecular-Targeted Regimen in a Three-Dimensional Neuroblastoma Spheroid Cell Culture Model.Cancers · 2023Article
- Genetic and Histopathological Heterogeneity of Neuroblastoma and Precision Therapeutic Approaches for Extremely Unfavorable Histology Subgroups.Biomolecules · 2022Review
- Mechanisms involved in selecting and maintaining neuroblastoma cancer stem cell populations, and perspectives for therapeutic targeting.World journal of stem cells · 2021Review
- Novel second-generation rexinoid induces growth arrest and reduces cancer cell stemness in human neuroblastoma patient-derived xenografts.Journal of pediatric surgery · 2021Article
- 9-cis-UAB30, a novel rexinoid agonist, decreases tumorigenicity and cancer cell stemness of human neuroblastoma patient-derived xenografts.Translational oncology · 2021Article
- Article
- Enhancing sustained-release local therapy: Single versus dual chemotherapy for the treatment of neuroblastoma.Surgery · 2020Article
- Cancer stem cells in neuroblastoma therapy resistance.Cancer drug resistance (Alhambra, Calif.) · 2019Article
- Replicating and identifying large cell neuroblastoma using high-dose intra-tumoral chemotherapy and automated digital analysis.Journal of pediatric surgery · 2019Article
- Heat Shock Proteins in Glioblastoma Biology: Where Do We Stand?International journal of molecular sciences · 2019Review
- Subgrouping of Unfavorable Histology Neuroblastomas With Immunohistochemistry Toward Precision Prognosis and Therapy Stratification.JCO precision oncology · 2019Article
- Cancer Stem Cells in Neuroblastoma: Expanding the Therapeutic Frontier.Frontiers in molecular neuroscience · 2019Review
- Developing preclinical models of neuroblastoma: driving therapeutic testing.BMC biomedical engineering · 2019Review
- Review
- MYCN induces neuroblastoma in primary neural crest cells.Oncogene · 2017Article
- Induced cancer stem cells generated by radiochemotherapy and their therapeutic implications.Oncotarget · 2017Review
- Retinoic acid and TGF-β signalling cooperate to overcome MYCN-induced retinoid resistance.Genome medicine · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer stem cells (CSCs) are plastic in nature, a characteristic that hampers cancer therapeutics. Neuroblastoma (NB) is a pediatric tumor of neural crest origin, and half of the cases are highly aggressive. By treating NB cell lines [SKNAS, SKNBE(2)C, CHP134, and SY5Y] with epigenetic modifiers for a short time, followed by sphere-forming culture conditions, we have established stem cell-like NB cells that are phenotypically stable for more than a year. These cells are characterized by their high expression of stemness factors, stem cell markers, and open chromatin structure. We referred to these cells as induced CSCs (iCSCs). SKNAS iCSC and SKNBE(2)C iCSC clones (as few as 100 cells) injected s.c. into SCID/Beige mice formed tumors, and in one case, SKNBE(2)C iCSCs metastasized to the adrenal gland, suggesting their increased metastatic potential. SKNAS iCSC xenografts showed the histologic appearance of totally undifferentiated large-cell NBs (LCNs), the most aggressive and deadly form of NB in humans. Immunohistochemical analyses showed that SKNAS iCSC xenografts expressed high levels of the stem cell marker CXCR4, whereas the SKNAS monolayer cell xenografts did not. The patterns of CXCR4 and MYC expression in SKNAS iCSC xenografts resembled those in the LCNs. The xenografts established from the NB iCSCs shared two common features: the LCN phenotype and high-level MYC/MYCN expression. These observations suggest both that NB cells with large and vesicular nuclei, representing their open chromatin structure, are indicative of stem cell-like tumor cells and that epigenetic changes may have contributed to the development of these most malignant NB cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.