LacZ transgene expression in the subcutaneous Dunn/LM8 osteosarcoma mouse model allows for the identification of
Matthias J E Arlt1, Ingo J Banke, Denise K Walters
1Department of Orthopedics, Balgrist University Hospital, University of Zürich, Zürich, Switzerland.
Abstract:
More effective treatment of patients with metastasizing osteosarcoma (OS) with a mean 5-year survival rate of <20% requires more detailed knowledge on the complex mechanisms of metastasis for the design of new drugs, which selectively target metastasizing cells. Moreover, novel diagnostic imaging technology for early detection of metastases is needed. Mouse models, which reproduce human metastasizing OS and allow visualization of single metastatic cells are instrumental for preclinical testing of new pharmaceuticals and diagnostic instruments. Here, the low metastatic Dunn cell line and its highly metastatic LM8 subline, both equipped with a constitutively expressed lacZ gene, were used to improve the well-established OS models in syngeneic C3H mice to achieve ex vivo visualization of single metastatic cells in affected organs by X-gal staining. These models, combined with a technique for in situ high quality lung tissue-maintaining perfusion revealed, as a novel finding, single metastasizing Dunn cells in lung and liver. Importantly, constitutive lacZ gene expression did not affect in vitro and in vivo tumorigenic and metastatic properties of Dunn and LM8 cells. Thus, these improved Dunn and LM8 OS mouse models will in the future serve as a benchmark for the development of new metastasis-targeting drugs and metastasis-imaging technology.
Insights
Developing improved mouse models for osteosarcoma (OS) metastasis is crucial for creating new drugs and diagnostic tools. These enhanced models allow for the visualization of single metastatic cells, aiding in the fight against this deadly cancer.
Area of Science:
- Oncology
- Translational Medicine
- Animal Models
Background:
- Metastatic osteosarcoma (OS) has a poor prognosis, with a 5-year survival rate below 20%.
- Effective treatment requires a deeper understanding of metastasis mechanisms and improved diagnostic tools for early detection.
- Current mouse models need enhancement for preclinical testing of novel therapeutics and imaging technologies.
Purpose of the Study:
- To develop improved osteosarcoma (OS) mouse models for visualizing single metastatic cells.
- To establish a benchmark for developing new metastasis-targeting drugs and imaging technologies for OS.
Main Methods:
- Utilized the low metastatic Dunn and highly metastatic LM8 osteosarcoma (OS) cell lines, engineered with a lacZ gene.
- Developed improved OS models in syngeneic C3H mice for ex vivo visualization of metastatic cells using X-gal staining.
- Employed in situ lung tissue-maintaining perfusion to visualize single metastatic cells in lung and liver.
Main Results:
- Successfully visualized single metastasizing Dunn cells in the lung and liver of improved OS mouse models.
- Confirmed that constitutive lacZ gene expression did not alter the tumorigenic or metastatic properties of Dunn and LM8 cells.
- Established enhanced OS mouse models capable of visualizing single metastatic cells.
Conclusions:
- The improved Dunn and LM8 osteosarcoma (OS) mouse models are valuable tools for preclinical research.
- These models will serve as a benchmark for developing novel drugs targeting OS metastasis and advanced imaging technologies.
- Further research using these models can significantly advance the treatment and diagnosis of metastatic OS.
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