ArticleThe American journal of pathology2010
Local mesenchymal stem/progenitor cells are a preferential target for initiation of adult soft tissue sarcomas associated with p53 and Rb deficiency.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- TP53 Loss Elevates NF-κB-IFN-β-MHC-Ia Signaling to Promote NK Cell Resistance in Osteosarcoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Keratin 5 marks cancer-propagating cells sustained by an osteopontin-producing niche in high-grade serous ovarian carcinoma.bioRxiv : the preprint server for biology · 2026Article
- Keratin 5 marks cancer-propagating cells sustained by an osteopontin-producing niche in high-grade serous ovarian carcinoma.Cancer heterogeneity and plasticity · 2026Article
- RB1 controls differentiation through positive regulation of phosphoglycerate mutases.Cell death & disease · 2025Article
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- Preclinical Models of Visceral Sarcomas.Biomolecules · 2023Review
- Retinoblastoma: present scenario and future challenges.Cell communication and signaling : CCS · 2023Review
- The Use of Hydrogels for the Treatment of Bone Osteosarcoma via Localized Drug-Delivery and Tissue Regeneration: A Narrative Review.Gels (Basel, Switzerland) · 2023Review
- Systemic Treatment of Soft Tissue Sarcomas in the Geriatric Population.Current treatment options in oncology · 2022Review
- TP53 in Biology and Treatment of Osteosarcoma.Cancers · 2021Review
- Article
- The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity.Oncogene · 2017Article
- Intersection of retinoblastoma tumor suppressor function, stem cells, metabolism, and inflammation.Cancer science · 2017Review
- Retinoblastoma tumor suppressor functions shared by stem cell and cancer cell strategies.World journal of stem cells · 2016Review
- A genetic platform to model sarcomagenesis from primary adult mesenchymal stem cells.Cancer discovery · 2015Article
- Merkel Cell Polyomavirus Small T Antigen Induces Cancer and Embryonic Merkel Cell Proliferation in a Transgenic Mouse Model.PloS one · 2015Article
- Multipotent Mesenchymal Stromal Cells: Possible Culprits in Solid Tumors?Stem cells international · 2015Review
- The differentiation stage of p53-Rb-deficient bone marrow mesenchymal stem cells imposes the phenotype of in vivo sarcoma development.Oncogene · 2013Article
- Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche.Nature · 2013Article
- The retinoblastoma protein (Rb) as an anti-apoptotic factor: expression of Rb is required for the anti-apoptotic function of BAG-1 protein in colorectal tumour cells.Cell death & disease · 2012Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The cell of origin and pathogenesis of the majority of adult soft tissue sarcomas (STS) remains poorly understood. Because mutations in both the P53 and RB tumor suppressor genes are frequent in STS in humans, we inactivated these genes by Cre-loxP-mediated recombination in mice with floxed p53 and Rb. Ninety-three percent of mice developed spindle cell/pleomorphic sarcomas after a single subcutaneous injection of adenovirus carrying Cre-recombinase. Similar to human STS, these sarcomas overexpress Cxcr4, which contributes to their invasive properties. Using irradiation chimeras generated by transplanting bone marrow cells from mice carrying either the Rosa26StoploxPLacZ or the Z/EG reporter, as well as the floxed p53 and Rb genes, into irradiated p53loxP/loxPRbloxP/loxP mice, it was determined that sarcomas do not originate from bone marrow-derived cells, such as macrophages, but arise from the local resident cells. At the same time, dermal mesenchymal stem cells isolated by strict plastic adherence and low levels of Sca-1 expression (Sca-1low, CD31negCD45neg) have shown enhanced potential for malignant transformation according to soft agar, invasion, and tumorigenicity assays, after the conditional inactivation of both p53 and Rb. Sarcomas formed after transplantation of these cells have features typical for undifferentiated high-grade pleomorphic sarcomas. Taken together, our studies indicate that local Sca-1low dermal mesenchymal stem/progenitor cells are preferential targets for malignant transformation associated with deficiencies in both p53 and Rb.
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