ArticleProceedings of the National Academy of Sciences of the United States of America2008
Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers.
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Who cites it
171 citing papers in PubMed, 266 citations in OpenAlex.
- An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy.Science advances · 2026Article
- Inherent tissue homeostasis of the juvenile metaphysis provides a foundation for osteosarcoma development.Nature communications · 2026Article
- Mevalonate pathway activation in Ewing sarcoma reveals a 3D-specific synergy between statins and BCL-xL inhibition.Molecular therapy. Oncology · 2026Article
- Murine osteosarcoma recapitulates the driver landscape and genomic complexity of osteosarcoma evolution in humans.bioRxiv : the preprint server for biology · 2026Article
- Review
- Skeletal stem cell lineages in osteosarcoma and bone metastasis.Journal of bone and mineral metabolism · 2026Review
- Molecular and Immune Mechanisms Governing Cancer Metastasis, Including Dormancy, Microenvironmental Niches, and Tumor-Specific Programs.International journal of molecular sciences · 2026Review
- Genetically Modified Mouse Models for Sarcoma Research: A Comprehensive Review.Current oncology reports · 2025Review
- Mouse Models of Osteosarcoma: Unraveling Disease Mechanisms and Accelerating Drug Discovery and Development.Cancer reports (Hoboken, N.J.) · 2025Review
- Clinical insights into circulating free-DNA in patients with bone sarcomas and ewing sarcoma.Clinics (Sao Paulo, Brazil) · 2025Article
- Primary Bone Tumors and Breast Cancer-Induced Bone Metastases: In Vivo Animal Models and New Alternative Approaches.Biomedicines · 2024Review
- Myc upregulates Ggct, γ-glutamylcyclotransferase to promote development of p53-deficient osteosarcoma.Cancer science · 2024Article
- Article
- PRRX1-TOP2A interaction is a malignancy-promoting factor in human malignant peripheral nerve sheath tumours.British journal of cancer · 2024Article
- WWOX promotes osteosarcoma development via upregulation of Myc.Cell death & disease · 2024Article
- Collagen type X expression and chondrocyte hypertrophic differentiation during OA and OS development.American journal of cancer research · 2024Review
- Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.Oncogene · 2023Article
- Review
- C/ebpα represses the oncogenic Runx3-Myc axis in p53-deficient osteosarcoma development.Oncogene · 2023Article
- Monitoring the Cell Cycle of Tumor Cells in Mouse Models of Human Cancer.Cold Spring Harbor perspectives in medicine · 2023Article
111 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.
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Registered trials
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.