Malignant astrocytomas originate from neural stem/progenitor cells in a somatic tumor suppressor mouse model
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Malignant astrocytomas are infiltrative and incurable brain tumors. Despite profound therapeutic implications, the identity of the cell (or cells) of origin has not been rigorously determined. We previously reported mouse models based on conditional inactivation of the human astrocytoma-relevant tumor suppressors p53, Nf1, and Pten, wherein through somatic loss of heterozygosity, mutant mice develop tumors with 100% penetrance. In the present study, we show that tumor suppressor inactivation in neural stem/progenitor cells is both necessary and sufficient to induce astrocytoma formation. We demonstrate in vivo that transformed cells and their progeny undergo infiltration and multilineage differentiation during tumorigenesis. Tumor suppressor heterozygous neural stem/progenitor cultures from presymptomatic mice show aberrant growth advantage and altered differentiation, thus identifying a pretumorigenic cell population.
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The incubation period of this model is in accordance with most other autochthonous models of medulloblastoma or adult glioma and may represent a fundamental aspect of brain cancer modeling in mice.
“However, this incubation period is in accordance with most, if not all, other autochthonous models of medulloblastoma or adult glioma and may represent a fundamental aspect of brain cancer modeling in mice (Alcantara Llaguno et al., 2009; Hill et al., 2015).”
From H3.3K27M Cooperates with Trp53 Loss and PDGFRA Gain in Mouse Embryonic Neural Progenitor Cells to Induce Invasive High-Grade Gliomas (2017) · cites this paper as Alcantara Llaguno et al., 2009
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- Authors
- Alcantara Llaguno, S., Chen, J., Kwon, C.-H., Jackson, E. L., Li, Y., Burns, D. K., Alvarez-Buylla, A., & Parada, L. F.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of California, San Francisco (US)
- Corresponding author
- Parada, Luis F.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 15
- Issue
- 1
- Pages
- 45-56
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC2650425
- OpenAlex
- W2014006702
- Cited by
- 694
- References
- 46
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 28 · 2023: 36 · 2022: 30 · 2021: 45 · 2020: 56 · 2019: 33 · 2018: 24 · 2017: 32 · 2016: 41 · 2015: 39 · 2014: 53 · 2013: 43 · 2012: 66
- FWCI
- 32.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Neurological Disorders and Stroke (P50NS052606)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- malignant astrocytoma, neural stem/progenitor cells, tumor cell of origin, loss of heterozygosity, p53, neurofibromatosis type 1, PTEN, conditional knockout mice, tumor infiltration, multilineage differentiation
- MeSH terms
- Adenoviridae, Aging, Animals, Astrocytoma, Cell Differentiation, Cell Transformation, Neoplastic, Disease Models, Animal, Genetic Vectors, Mice, Transgenic, Neurons, Precancerous Conditions, Stem Cells, Gene Expression Regulation, Neoplastic, Survival Rate, Integrases, Tumor Suppressor Proteins, Mice
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