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Updated: Jul 16, 2026

A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
The IL-17-IL-17RA axis is required to promote osteosarcoma progression in mice
Naoto Yoshimura1, Ryusho Kariya2,3, Masaki Shimada1
1Department of Orthopedic Surgery, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto, 860-8556, Japan.
Abstract:
Osteosarcoma is rare but is the most common bone tumor. Diagnostic tools such as magnetic resonance imaging development of chemotherapeutic agents have increased the survival rate in osteosarcoma patients, although 5-year survival has plateaued at 70%. Thus, development of new treatment approaches is needed. Here, we report that IL-17, a proinflammatory cytokine, increases osteosarcoma mortality in a mouse model with AX osteosarcoma cells. AX cell transplantation into wild-type mice resulted in 100% mortality due to ectopic ossification and multi-organ metastasis. However, AX cell transplantation into IL-17-deficient mice significantly prolonged survival relative to controls. CD4-positive cells adjacent to osteosarcoma cells express IL-17, while osteosarcoma cells express the IL-17 receptor IL-17RA. Although AX cells can undergo osteoblast differentiation, as can patient osteosarcoma cells, IL-17 significantly inhibited that differentiation, indicating that IL-17 maintains AX cells in the undifferentiated state seen in malignant tumors. By contrast, IL-17RA-deficient mice transplanted with AX cells showed survival comparable to wild-type mice transplanted with AX cells. Biopsy specimens collected from osteosarcoma patients showed higher expression of IL-17RA compared to IL-17. These findings suggest that IL-17 is essential to maintain osteosarcoma cells in an undifferentiated state and could be a therapeutic target for suppressing tumorigenesis.
Insights
Interleukin-17 (IL-17) promotes osteosarcoma progression and mortality by inhibiting osteoblast differentiation. Targeting IL-17 may offer a new therapeutic strategy for this common bone cancer.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Osteosarcoma is the most common primary bone tumor, with a 5-year survival rate of 70% despite advances in chemotherapy.
- New therapeutic strategies are needed to improve outcomes for osteosarcoma patients.
Purpose of the Study:
- To investigate the role of interleukin-17 (IL-17) in osteosarcoma progression and mortality.
- To explore IL-17 as a potential therapeutic target for osteosarcoma.
Main Methods:
- Utilized a mouse model of osteosarcoma with AX osteosarcoma cells.
- Compared survival rates in wild-type, IL-17-deficient, and IL-17 receptor-deficient (IL-17RA) mice.
- Analyzed IL-17 and IL-17RA expression in tumor tissues and patient biopsy specimens.
- Assessed the effect of IL-17 on osteosarcoma cell differentiation.
Main Results:
- IL-17 significantly increased osteosarcoma mortality in mice, leading to ectopic ossification and metastasis.
- IL-17-deficient mice showed significantly prolonged survival compared to controls.
- IL-17 inhibited osteoblast differentiation of osteosarcoma cells, maintaining their undifferentiated state.
- IL-17RA-deficient mice exhibited survival rates comparable to wild-type mice.
- Patient osteosarcoma samples showed higher IL-17RA expression than IL-17.
Conclusions:
- IL-17 plays a critical role in maintaining osteosarcoma cells in an undifferentiated, malignant state.
- IL-17 signaling is essential for osteosarcoma progression and mortality.
- Targeting the IL-17 pathway presents a promising therapeutic avenue for osteosarcoma treatment.
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