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Updated: Feb 23, 2026

Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Fractalkine/CX3CL1 induced intercellular adhesion molecule-1-dependent tumor metastasis through the
Ju-Fang Liu1, Ya-Ting Tsao2, Chun-Han Hou2
1Central Laboratory, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Abstract:
Osteosarcoma is the most common primary bone tumor in children and teens. The exact molecular mechanism underlying osteosarcoma progression still remains unclear. The CX3CL1/fractalkine has been implicated in various tumors but not in osteosarcoma. This study is the first to show that fractalkine promotes osteosarcoma metastasis by promoting cell migration. Fractalkine expression was higher in osteosarcoma cell lines than in normal osteoblasts. Fractalkine induced cell migration by upregulating intercellular adhesion molecule-1 (ICAM-1) expression via CX3CR1/PI3K/Akt/NF-κB pathway in human osteosarcoma cells. Knockdown of fractalkine expression markedly inhibited cell migration and lung metastasis in osteosarcoma. Finally, we showed a clinical correlation between CX3CL1 expression and ICAM-1 expression as well as tumor stage in human osteosarcoma tissues. In conclusion, our results indicate that fractalkine promotes cell migration and metastasis of osteosarcoma by upregulating ICAM-1 expression. Thus, fractalkine could serve a novel therapeutic target for preventing osteosarcoma metastasis.
Insights
Fractalkine (CX3CL1) drives osteosarcoma metastasis by increasing cell migration and upregulating ICAM-1. Targeting fractalkine may prevent bone cancer spread.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Osteosarcoma is the most common pediatric bone cancer.
- Molecular mechanisms of osteosarcoma progression are not fully understood.
- CX3CL1/fractalkine's role in osteosarcoma is uninvestigated.
Purpose of the Study:
- To investigate the role of CX3CL1/fractalkine in osteosarcoma.
- To determine if fractalkine influences osteosarcoma cell migration and metastasis.
Main Methods:
- Compared fractalkine expression in osteosarcoma vs. normal cells.
- Investigated fractalkine's effect on cell migration via the CX3CR1/PI3K/Akt/NF-κB pathway.
- Analyzed ICAM-1 expression changes.
- Assessed the impact of fractalkine knockdown on metastasis in vivo.
- Correlated CX3CL1 and ICAM-1 expression with clinical tumor stage.
Main Results:
- Fractalkine expression is elevated in osteosarcoma.
- Fractalkine significantly enhances osteosarcoma cell migration by upregulating ICAM-1.
- The CX3CR1/PI3K/Akt/NF-κB pathway mediates fractalkine-induced migration.
- Knockdown of fractalkine reduces cell migration and lung metastasis.
- Clinical data show a correlation between CX3CL1, ICAM-1, and tumor stage.
Conclusions:
- Fractalkine promotes osteosarcoma cell migration and metastasis.
- Upregulation of ICAM-1 is a key mechanism.
- CX3CL1/fractalkine represents a potential therapeutic target for osteosarcoma metastasis.
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