A nude mouse model of human osteosarcoma lung metastases for evaluating new therapeutic strategies
S F Jia1, L L Worth, E S Kleinerman
1Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston 77030, USA.
Abstract:
The purpose of these studies was to develop a metastatic osteosarcoma nude mouse model to evaluate the in vivo efficacy of new therapeutic compounds. Human SAOS-2 osteosarcoma cells (10(6) cells) were injected i.v. into nude mice. Cells isolated from a rare pulmonary metastases 6 months later were established (SAOS-LM1) in culture and re-injected. This procedure was repeated 5 additional times to produce the SAOS-LM6 cell line. Visible pulmonary nodules were present 8 weeks following i.v. injection of 10(6) SAOS-LM6 cells as compared to 17 weeks using SAOS-LM2 cells. Microscopic SAOS-LM6 pulmonary metastases were demonstrated at 6 weeks. Administration of adriamycin on week 9 resulted in regression of macroscopic SAOS-LM6 lung tumors. The ability of the model to be used to evaluate the effectiveness of a biologic agent against microscopic disease was also verified. It was concluded that this model can assess therapeutic efficacy and therefore, may have a role in investigating the potential of novel approaches aimed at eliminating pulmonary metastatic osteosarcoma.
Insights
Researchers developed a novel osteosarcoma mouse model to test new cancer therapies. This model effectively simulates pulmonary metastases, aiding in the evaluation of treatments for osteosarcoma lung spread.
Area of Science:
- Oncology
- Preclinical Research
- Animal Models
Background:
- Osteosarcoma is a primary bone cancer with a high propensity for metastasis, particularly to the lungs.
- Developing reliable preclinical models is crucial for evaluating novel therapeutic strategies against metastatic osteosarcoma.
Purpose of the Study:
- To establish a reproducible nude mouse model of metastatic osteosarcoma.
- To assess the in vivo efficacy of therapeutic compounds against pulmonary osteosarcoma metastases.
- To validate the model's utility for evaluating treatments for both macroscopic and microscopic disease.
Main Methods:
- Human SAOS-2 osteosarcoma cells were intravenously injected into nude mice.
- Cells from pulmonary metastases were isolated, cultured (SAOS-LM1), and re-injected iteratively to generate the SAOS-LM6 cell line.
- Tumor development and response to adriamycin treatment were monitored.
Main Results:
- The SAOS-LM6 cell line produced visible pulmonary nodules by 8 weeks post-injection, significantly faster than SAOS-LM2 cells (17 weeks).
- Microscopic pulmonary metastases were detectable as early as 6 weeks.
- Adriamycin administration led to the regression of macroscopic lung tumors.
- The model demonstrated efficacy in evaluating treatments for microscopic disease.
Conclusions:
- A robust nude mouse model for pulmonary metastatic osteosarcoma was successfully developed using the SAOS-LM6 cell line.
- This model is suitable for assessing the therapeutic efficacy of novel compounds against osteosarcoma lung metastases.
- The model holds potential for investigating new therapeutic approaches to eliminate pulmonary metastatic osteosarcoma.
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