Related Experiment Video
Updated: May 26, 2026
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
[Retros Flt-1 decelerates the growth of a murine experimental osteosarcoma]
Xiao-tang Xin1, De-zhen Yin, Hai Lan
1Department of Orthopaedic Surgery, Weihai Municipal Hospital, Weihai, China.
Objective:
To examine the influence of vascular endothelial growth factors (VEGF) in controlling the growth of an experimental osteosarcoma in mice by performing retrovirus-mediated sFlt-1 gene modification.
Methods:
From March to October 2010 human osteosarcoma G-292 cells were in vitro infected with retroviral vectors encoding soluble Flt-1 or LacZ gene before transplanted into proximal tibiae of immune deficient SCID mice to establish experimental orthotopic osteosarcoma. Daily observation and biweekly microCT were performed to monitor tumor development and progression till sacrifice at 8 weeks after tumor cell inoculation for histological and molecular analyses.
Results:
Successful transgene expression was confirmed in the culture media of sFlt-1 transduced G-292 cells using ELISA, and with positive X-gal staining of the LacZ transduced cells. Noteworthy tumors were grown in all mice on the tibiae receiving G-292 cell inoculation, with clear detection on microCT images starting 2 weeks after inoculation. Over the time period, tumors derived from sFlt-1 transduced G-292 cells were distinctively smaller in size compared to the ones from wide-type G-292 and G-292-LacZ cells. Histology showed typical osteosarcoma characteristics including severe cellular pleomorphism, bone erosions, and neo-vascularization. Real-time polymerase chain reaction indicated significantly higher sFlt-1 expression in sFlt-1 transduced groups than the wild-type G-292 or LacZ treated groups. Strong expression of oncogenes c-myc and c-fos were also obvious, along with the expression of VEGF in the primary tumor tissue.
Conclusion:
Retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.
Insights
Retrovirus-mediated soluble Fms-like tyrosine kinase-1 (sFlt-1) gene modification significantly decelerated experimental osteosarcoma tumor growth in a murine model. This study highlights sFlt-1's potential in controlling osteosarcoma progression.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Context:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Vascular endothelial growth factors (VEGF) play a crucial role in tumor angiogenesis and progression.
- Targeting VEGF signaling is a potential therapeutic strategy for osteosarcoma.
Purpose:
- To investigate the effect of retrovirus-mediated soluble Fms-like tyrosine kinase-1 (sFlt-1) gene modification on experimental osteosarcoma growth in mice.
- To assess the impact of sFlt-1 on tumor size, histology, and molecular markers in an orthotopic osteosarcoma model.
Summary:
- Human osteosarcoma cells (G-292) were modified with retroviral vectors encoding sFlt-1 or LacZ and transplanted into SCID mice.
- Tumor growth was monitored using microCT, with sFlt-1 modified tumors showing significantly smaller sizes compared to controls.
- Histological and molecular analyses confirmed osteosarcoma characteristics and elevated sFlt-1 expression in the treated group.
Impact:
- Retrovirus-mediated sFlt-1 gene modification demonstrates a therapeutic potential to decelerate osteosarcoma tumor growth.
- This finding supports further investigation of VEGF pathway inhibition as a strategy for osteosarcoma treatment.
- The study provides a preclinical basis for developing gene-based therapies targeting angiogenesis in bone cancers.
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