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Updated: Jun 15, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
An orthotopic, postsurgical model of luciferase transfected murine osteosarcoma with spontaneous metastasis
Joseph L Sottnik1, Dawn L Duval, E J Ehrhart
1Animal Cancer Center, Department of Clinical Sciences, Colorado State University, Fort Collins, CO 80523, USA. jsottnik@rams.colostate.edu
Abstract:
Osteosarcoma (OS) is the most common bone tumor in humans. Newer, more clinically relevant models of OS are required to investigate novel therapeutics. The ability to study spontaneous micrometastases in the absence of a primary tumor is important since this is the manner in which most patients are treated clinically. Therefore, we have developed a novel model of murine OS using the DLM8 cell line, which is syngeneic to C3H mice. We have engineered these cells to express firefly luciferase so the development of metastases can be followed serially and non-invasively. These cells form osteolytic/osteoproductive lesions and metastasize spontaneously after orthotopic implantation in the proximal tibia, and the development of soft-tissue metastasis can be followed serially by luciferase expression following amputation. We have demonstrated a significant prolongation of disease-free and overall survival in the surgical adjuvant setting following treatment with doxorubicin or carboplatin, drugs which form the mainstay of treatment for human OS. In conclusion, we have developed a novel surgical adjuvant model of metastatic OS in immunocompetent mice that closely recapitulates the clinical situation, allowing the evaluation of novel therapeutics in the context of minimal residual disease.
Insights
Researchers developed a new mouse model for osteosarcoma (OS) to study metastasis. This model accurately mimics human OS treatment, aiding the development of new therapies for minimal residual disease.
Area of Science:
- Oncology
- Preclinical Cancer Models
- Surgical Oncology
Background:
- Osteosarcoma (OS) is the most common primary bone cancer in humans.
- Current preclinical models often fail to fully replicate the clinical scenario of metastatic OS.
- There is a critical need for advanced models to study micrometastases and test novel therapeutics.
Purpose of the Study:
- To develop and validate a novel, clinically relevant murine model of metastatic osteosarcoma.
- To enable non-invasive, serial monitoring of spontaneous micrometastases.
- To assess the efficacy of standard chemotherapeutics in a surgical adjuvant setting.
Main Methods:
- Development of a luciferase-expressing DLM8 murine osteosarcoma cell line, syngeneic to C3H mice.
- Orthotopic implantation into the proximal tibia to induce osteolytic/osteoproductive lesions and spontaneous metastasis.
- Serial monitoring of metastasis via luciferase imaging post-amputation.
- Evaluation of doxorubicin and carboplatin in the surgical adjuvant setting.
Main Results:
- The novel model forms osteolytic/osteoproductive lesions and metastasizes spontaneously.
- Luciferase expression allows non-invasive, serial tracking of soft-tissue metastasis.
- Surgical adjuvant treatment with doxorubicin or carboplatin significantly improved disease-free and overall survival.
- The model recapitulates key aspects of human osteosarcoma clinical progression and treatment.
Conclusions:
- A novel surgical adjuvant model of metastatic osteosarcoma in immunocompetent mice has been successfully developed.
- This model closely mimics the clinical situation, particularly minimal residual disease.
- It provides a valuable platform for evaluating novel therapeutic strategies in osteosarcoma.
