Related Experiment Video
Updated: Mar 28, 2026
A Syngeneic Orthotopic Osteosarcoma Sprague Dawley Rat Model with Amputation to Control Metastasis Rate
Published on: May 3, 2021
Effect of recombinant human bone morphogenetic protein-2 on a novel lung cancer spine metastasis model in rodents
Kevin A Sonn1, Abhishek S Kannan1, Sharath S Bellary1
1Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois.
Abstract:
Lung cancer is the second most prevalent cancer. Spinal metastases are found in 30-90% of patients with death attributed to cancer. Due to bony destruction caused by metastases, surgical intervention is often required to restore spinal alignment and stability. While some research suggests that BMP-2 may possess tumorigenic effects, other studies show possible inhibition of cancer growth. Thirty-six athymic rats underwent intraosseous injection of lung adenocarcinoma cells into the L5 vertebral body. Cells were pre-treated with vehicle control (Group A) or rhBMP-2 (Group B) prior to implantation. At 4 weeks post-implantation, in vivo bioluminescent imaging (BLI) was performed to confirm presence of tumor and quantify signal. Plain radiographs and microComputed Tomography (microCT) were employed to establish and quantitate osteolysis. Histological analysis characterized pathologic changes in the vertebral body. At 4 weeks post-implantation, BLI showed focal signal in the L5 vertebral body in 93% of Group A animals and 89% of Group B animals. Average tumor burden by BLI radiance was 7.43 × 10(3) p/s/cm(2) /sr (Group A) and 1.11 × 10(4) p/s/cm(2) /sr (Group B). Radiographs and microCT demonstrated osteolysis in 100% of animals showing focal BLI signal. MicroCT demonstrated significant bone loss in both groups compared to age-matched controls but no difference between study groups. Histological analysis confirmed tumor invasion in the L5 vertebral body. These findings provide a reliable in vivo model to study isolated spinal metastases from lung cancer. Statement of Clinical Significance: The data support the notion that exposure to rhBMP-2 does not promote the growth of A549 lung cancer spine lesions. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1274-1281, 2016.
Insights
This study found that recombinant human bone morphogenetic protein-2 (rhBMP-2) does not promote the growth of lung cancer spinal metastases in an athymic rat model. The findings suggest rhBMP-2 is safe for use in patients with spinal tumors.
Area of Science:
- Orthopaedic Research
- Oncology
- Biomedical Engineering
Background:
- Lung cancer frequently metastasizes to the spine, causing bone destruction and necessitating surgical intervention.
- The role of bone morphogenetic protein-2 (BMP-2) in cancer growth is debated, with some studies suggesting a tumorigenic role and others indicating an inhibitory effect.
- Understanding BMP-2's effect on spinal metastases is crucial for managing lung cancer patients with bone involvement.
Purpose of the Study:
- To establish a reliable in vivo model for studying lung cancer spinal metastases.
- To investigate the effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the growth and osteolytic activity of lung adenocarcinoma cells in the L5 vertebral body of athymic rats.
Main Methods:
- Thirty-six athymic rats received intraosseous injections of lung adenocarcinoma cells pre-treated with either vehicle control or rhBMP-2 into the L5 vertebral body.
- In vivo bioluminescent imaging (BLI) was used to confirm tumor presence and quantify tumor burden.
- Plain radiographs and microComputed Tomography (microCT) were employed to assess osteolysis, and histological analysis characterized pathological changes.
Main Results:
- Tumor formation was observed in 93% of control group animals and 89% of rhBMP-2 treated animals.
- Both groups exhibited significant osteolysis compared to controls, with no significant difference in tumor burden or bone loss between the groups.
- Histological analysis confirmed tumor invasion in the L5 vertebral body in all analyzed samples.
Conclusions:
- The developed in vivo model reliably replicates lung cancer spinal metastases.
- Exposure to rhBMP-2 did not enhance the growth or osteolytic potential of A549 lung cancer cells in the spinal metastatic model.
- These findings suggest that rhBMP-2 may not promote the progression of lung cancer spinal metastases.
