Related Experiment Video
Updated: Jul 3, 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
VEGF blockade decelerates the growth of a murine experimental osteosarcoma
Dezhen Yin1, Tanghong Jia, Weiming Gong
1Shandong University School of Medicine, Jinan 250010, PR China.
Abstract:
Retrovirus-mediated sFlt-1 gene modification was performed to examine the influence of VEGF in controlling the growth of an experimental osteosarcoma in mice. 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. 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 when 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. Overall, data suggest that retrovirus-mediated sFLT-1 gene modification decelerates the osteosarcoma tumor growth in this murine model.
Insights
Gene modification using soluble Flt-1 (sFlt-1) in osteosarcoma cells slowed tumor growth in a mouse model. This study explored vascular endothelial growth factor (VEGF) inhibition's role in controlling experimental osteosarcoma progression.
Area of Science:
- Oncology
- Gene Therapy
- Vascular Biology
Background:
- Osteosarcoma is a primary bone malignancy with limited treatment options.
- Vascular endothelial growth factor (VEGF) plays a crucial role in tumor angiogenesis and progression.
- Soluble Flt-1 (sFlt-1) is a VEGF inhibitor that can potentially suppress tumor growth.
Purpose of the Study:
- To investigate the effect of retrovirus-mediated sFlt-1 gene modification on experimental osteosarcoma growth in mice.
- To assess the role of VEGF inhibition in controlling osteosarcoma development.
Main Methods:
- Human osteosarcoma G-292 cells were transduced with retroviral vectors encoding sFlt-1 or LacZ.
- Cells were implanted into the tibiae of immunocompromised SCID mice to establish orthotopic osteosarcoma models.
- Tumor growth was monitored using microCT, followed by histological and molecular analyses.
Main Results:
- Successful transduction and expression of sFlt-1 and LacZ genes were confirmed.
- Tumors derived from sFlt-1 transduced cells were significantly smaller compared to control groups (wild-type and LacZ).
- Histological analysis revealed typical osteosarcoma features, and molecular analysis showed increased sFlt-1 expression and elevated oncogene expression (c-myc, c-fos) alongside VEGF.
Conclusions:
- Retrovirus-mediated sFlt-1 gene modification effectively decelerates osteosarcoma tumor growth in a murine model.
- VEGF inhibition via sFlt-1 holds therapeutic potential for osteosarcoma treatment.
- Further research is warranted to explore sFlt-1 as a therapeutic strategy for osteosarcoma.
