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SDF-1/CXCR4 promotes F5M2 osteosarcoma cell migration by activating the Wnt/β-catenin signaling pathway
Yao Lu1, Bin Hu, Guo-Feng Guan
1Department of Orthopaedic Surgery, Tangdu Hospital, The Fourth Military Medical University, 569 Xin Si Road, Xi'an, 710038, Shaanxi, China.
Abstract:
Osteosarcoma (OS), the most common primary malignant bone tumor in children and adolescents, lacks an effective therapy. Stromal cell-derived factor (SDF-1) and its receptor, CXCR4, play multiple roles in migration, proliferation, and survival of different tumor cells. This study aimed to investigate whether the functional SDF-1/CXCR4 signaling mediates chemotaxis in F5M2 OS cells as well as the underlying mechanisms. Immunohistochemistry and immunofluorescence microscopy were used. RNA expression was detected by real-time quantitative polymerase chain reaction, and protein expression was examined by Western blotting. Migration assays were carried out in F5M2 cells. The results showed that the expression of CXCR4 and β-catenin mRNA and protein was significantly higher in OS tissues compared to the surrounding non-neoplastic tissues. SDF-1 promoted F5M2 cell migration by activating the AKT and Wnt/β-catenin signaling pathway, which was abrogated by preincubation with AMD3100 and LY294002. In conclusion, SDF-1/CXCR4 axis-promoted F5M2 cell migration was regulated by the Wnt/β-catenin signaling pathway.
Insights
Stromal cell-derived factor (SDF-1) promotes osteosarcoma (OS) cell migration by activating the Wnt/β-catenin pathway. Targeting the SDF-1/CXCR4 axis may offer a new therapeutic strategy for this bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Osteosarcoma (OS) is a primary malignant bone tumor in children and adolescents with limited effective treatments.
- The stromal cell-derived factor (SDF-1)/CXCR4 axis is implicated in tumor cell migration, proliferation, and survival.
Purpose of the Study:
- To investigate the role of SDF-1/CXCR4 signaling in mediating chemotaxis in F5M2 OS cells.
- To elucidate the underlying molecular mechanisms involved in SDF-1-induced OS cell migration.
Main Methods:
- Immunohistochemistry and immunofluorescence microscopy for protein expression.
- Real-time quantitative polymerase chain reaction for RNA expression.
- Western blotting for protein analysis and migration assays.
Main Results:
- CXCR4 and β-catenin mRNA and protein expression were significantly elevated in OS tissues compared to non-neoplastic tissues.
- SDF-1 significantly promoted F5M2 cell migration.
- SDF-1-induced migration was dependent on the activation of AKT and Wnt/β-catenin signaling pathways.
Conclusions:
- The SDF-1/CXCR4 axis promotes F5M2 osteosarcoma cell migration.
- This migratory process is regulated by the Wnt/β-catenin signaling pathway.
- Inhibition of SDF-1/CXCR4 signaling abrogated SDF-1-induced migration, suggesting therapeutic potential.
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