Related Experiment Video
Updated: Jul 1, 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
scFv-mediated delivery of truncated BID suppresses HER2-positive osteosarcoma growth and metastasis
Le-Qun Shan1, Xiu-Chun Qiu, Yan-Ming Xu
1Department of Orthopaedics Surgery, Tangdu Hospital, Xi'an, China.
Abstract:
Osteosarcoma is the most common primary malignant bone tumor, with high rates of metastasis. Here, we examined the expression of human epidermal growth factor receptor-2 (HER-2) in osteosarcoma cell lines with different metastatic potential, finding that the expression was correlated with metastasis of implanted tumors. We then introduced an expression vector encoding the e23sFv-PEA II-Bid Delta1-60 gene, composed of a HER2-specific single-chain antibody fused with domain II of Pseudomonas exotoxin A (PEA) and the carboxy end of truncated active Bid. We demonstrated that the e23sFv-PEA II-Bid Delta1-60 molecule selectively recognized and killed HER2-overexpressing osteosarcoma cells in vitro. Subsequently, we introduced the e23sFv-PEA II-bid Delta1-60 gene into BALB/c athymic mice bearing HER2-positive osteosarcomas using i.m. injections of liposome-encapsulated vector. Expression of the e23sFv-PEA II-Bid Delta1-60 gene suppressed tumor growth, significantly prolonged animal survival and inhibited metastasis, thereby suggesting it may represent a competitive approach to treating HER2/neu-positive osteosarcoma.
Insights
This study shows that targeting human epidermal growth factor receptor-2 (HER-2) with a novel gene therapy can effectively inhibit osteosarcoma growth and metastasis in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Gene Therapy
Background:
- Osteosarcoma is the most common primary bone cancer, characterized by high metastatic rates.
- Human epidermal growth factor receptor-2 (HER-2) expression is implicated in osteosarcoma metastasis.
- Targeting HER-2 presents a potential therapeutic strategy for osteosarcoma.
Purpose of the Study:
- To investigate the correlation between HER-2 expression and osteosarcoma metastasis.
- To develop and evaluate a novel gene-based therapeutic agent targeting HER-2.
- To assess the efficacy of this agent in suppressing tumor growth and metastasis in vivo.
Main Methods:
- Examined HER-2 expression in osteosarcoma cell lines with varying metastatic potentials.
- Constructed an expression vector encoding the e23sFv-PEA II-Bid Delta1-60 gene targeting HER-2.
- Administered liposome-encapsulated vector via intramuscular injection in mice with HER2-positive osteosarcomas.
Main Results:
- HER-2 expression correlated with the metastatic potential of implanted osteosarcoma tumors.
- The e23sFv-PEA II-Bid Delta1-60 molecule selectively killed HER2-overexpressing osteosarcoma cells in vitro.
- Gene expression suppressed tumor growth, prolonged survival, and inhibited metastasis in vivo.
Conclusions:
- The e23sFv-PEA II-Bid Delta1-60 gene therapy effectively targets and inhibits HER2-positive osteosarcoma.
- This approach shows promise as a novel treatment strategy for HER2/neu-positive osteosarcoma.
- Further investigation is warranted to explore its clinical applicability.
