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Peer-reviewedCC BYScience Advances

An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy

  • Taiana C. Leite1,2,3
  • Jue Hou4
  • Xuehui Geng2,3
  • Luigi Mancinelli2,3
  • Abigail Sedlacek5
  • Devanshi A. Nayak5
  • Karen E. Schoedel6
  • Kurt R. Weiss7,8
  • Robert J. Binder5
  • Charles P. Lin4
  • Giuseppe Intini2,3,7,9,10
10 affiliations
  1. 1Department of Oral and Craniofacial Sciences, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA.
  2. 2Department of Periodontics and Preventive Dentistry, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA.
  3. 3Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, Pittsburgh, PA, USA.
  4. 4Center for Systems Biology and Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
  5. 5Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  6. 6Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  7. 7Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  8. 8Department of Orthopaedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  9. 9Pittsburgh Center for Interdisciplinary Bone and Mineral Research, University of Pittsburgh, Pittsburgh, PA, USA.
  10. 10Department of Medicine, Division of Hematology and Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
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Abstract

Despite substantial treatment improvements, the 5-year survival rate for metastatic osteosarcoma (OS) is still as low as 20%. Immunocompetent genetic mouse models of OS have been introduced, enabling in vivo OS studies. Here, we present the ROCCIA mouse, a quintuple-mutant extension of these models that develops multifluorescent OS tumors, allowing distinct fluorescently labeled OS cell populations to be identified and traced both within tumors and in the circulation. In addition, this model enables postnatal inactivation of the p53 and Rb1 genes, thus resembling development and progression of OS in humans. Using this model, we show that osterix ( Osx )–expressing fluorescent tumor cells appear in circulation upon OS development and predominate in lung metastases, thus representing a potential target for future therapies. We also show that the immunological landscape of this model’s tumor microenvironment mimics the previously described human OS microenvironment. Therefore, this immunocompetent, quintuple mutant, multifluorescent mouse model represents a powerful resource to analyze OS tumor development and metastasis in real time and to test translational therapies.

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Cite

BibTeXRIS
BibTeX
@article{leite2026immunocompetent,
  title = {{An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy}},
  author = {Taiana C. Leite and Jue Hou and Xuehui Geng and Luigi Mancinelli and Abigail Sedlacek and Devanshi A. Nayak and Karen E. Schoedel and Kurt R. Weiss and Robert J. Binder and Charles P. Lin and Giuseppe Intini},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aed6938},
  url = {https://www.science.org/doi/10.1126/sciadv.aed6938},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - An immunocompetent, multifluorescent resource for real-time analysis of osteosarcoma progression, metastasis, and response to therapy
AU  - Taiana C. Leite
AU  - Jue Hou
AU  - Xuehui Geng
AU  - Luigi Mancinelli
AU  - Abigail Sedlacek
AU  - Devanshi A. Nayak
AU  - Karen E. Schoedel
AU  - Kurt R. Weiss
AU  - Robert J. Binder
AU  - Charles P. Lin
AU  - Giuseppe Intini
PY  - 2026
DA  - 2026/10/02
JO  - Science Advances
DO  - 10.1126/sciadv.aed6938
UR  - https://www.science.org/doi/10.1126/sciadv.aed6938
AB  - Despite substantial treatment improvements, the 5-year survival rate for metastatic osteosarcoma (OS) is still as low as 20%. Immunocompetent genetic mouse models of OS have been introduced, enabling in vivo OS studies. Here, we present the ROCCIA mouse, a quintuple-mutant extension of these models that develops multifluorescent OS tumors, allowing distinct fluorescently labeled OS cell populations to be identified and traced both within tumors and in the circulation. In addition, this model enables postnatal inactivation of the p53 and Rb1 genes, thus resembling development and progression of OS in humans. Using this model, we show that osterix ( Osx )–expressing fluorescent tumor cells appear in circulation upon OS development and predominate in lung metastases, thus representing a potential target for future therapies. We also show that the immunological landscape of this model’s tumor microenvironment mimics the previously described human OS microenvironment. Therefore, this immunocompetent, quintuple mutant, multifluorescent mouse model represents a powerful resource to analyze OS tumor development and metastasis in real time and to test translational therapies.
SN  - 2375-2548
ER  -