| RRC ID |
86554
|
| 著者 |
Gospos J, Laubach M, Savi FM, Ravichandran A, Bauer J, Friedrich O, Holzapfel BM, Wagner F, Mashimo T, Saifzadeh S, Hutmacher DW, McGovern JA.
|
| タイトル |
Dynamic assessment of a humanized bone tumour microenvironment reveals insights into osteosarcoma primary tumour remodelling and lung metastases.
|
| ジャーナル |
Sci Rep
|
| 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.
|
| 巻・号 |
15(1)
|
| ページ |
45619
|
| 公開日 |
2025-11-28
|
| DOI |
10.1038/s41598-025-29941-z
|
| PII |
10.1038/s41598-025-29941-z
|
| PMID |
41315643
|
| PMC |
PMC12753712
|
| MeSH |
Animals
Bone Neoplasms* / metabolism
Bone Neoplasms* / pathology
Cell Line, Tumor
Disease Models, Animal
Humans
Lung Neoplasms* / pathology
Lung Neoplasms* / secondary
Osteosarcoma* / metabolism
Osteosarcoma* / pathology
Rats
Tumor Microenvironment*
|
| リソース情報 |
| ラット |
F344-Il2rgem1IexasRag2em1Iexas (StrainID=1300) |
