Dynamic assessment of a humanized bone tumour microenvironment reveals insights into osteosarcoma primary tumour remodelling and lung metastases
Gospos J, Laubach M, Savi FM, Ravichandran A, Bauer J, Friedrich O, Holzapfel BM, Wagner F, Mashimo T, Saifzadeh S, Hutmacher DW, McGovern JA (2025)
Publication Type: Journal article
Publication year: 2025
Journal
Book Volume: 15
Article Number: 45619
Journal Issue: 1
DOI: 10.1038/s41598-025-29941-z
Abstract
Osteosarcoma (OS) is the most common primary bone cancer in children and adolescents, with poor prognosis linked to metastasis and recurrence. Preclinical models that replicate human disease progression and the tumour microenvironment (TME) are critical for advancing therapies. We developed a novel orthotopic and humanised bone tumour microenvironment model in highly immunocompromised Il2rg and Rag2 double knockout rats. A humanised bone niche (HN) was established by implanting orthotopic humanised bone constructs (ohTEBCs) around the rat femur, followed by SaOS-2-luc cell injection. Longitudinal µCT and bioluminescent imaging tracked HN formation, tumour growth, and metastasis. Histological and immunohistochemical analyses revealed pathological mineralisation, extensive collagen deposition, tumour-specific ECM production, and neovascularisation within primary tumours and lung metastases. This model supports consistent engraftment of SaOS-2-luc tumours with robust metastatic spread, recapitulating key human OS features. It offers a translatable preclinical platform for studying OS progression and testing chemotherapy and surgical interventions.
Involved external institutions
Queensland University of Technology (QUT)
Australia (AU)
Klinikum der Universität München (LMU Klinikum)
Germany (DE)
University of Tokyo
Japan (JP)
Australia (AU)
Klinikum der Universität München (LMU Klinikum)
Germany (DE)
University of Tokyo
Japan (JP)
How to cite
APA:
Gospos, J., Laubach, M., Savi, F.M., Ravichandran, A., Bauer, J., Friedrich, O.,... McGovern, J.A. (2025). Dynamic assessment of a humanized bone tumour microenvironment reveals insights into osteosarcoma primary tumour remodelling and lung metastases. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-29941-z
MLA:
Gospos, Jonathan, et al. "Dynamic assessment of a humanized bone tumour microenvironment reveals insights into osteosarcoma primary tumour remodelling and lung metastases." Scientific Reports 15.1 (2025).
BibTeX: Download