Zebrafish Osteosarcoma Models

Introduction

Osteosarcoma is the most common primary malignant bone tumor, primarily affecting children, adolescents, and young adults during periods of rapid skeletal growth. The disease originates from malignant mesenchymal cells capable of producing osteoid matrix and is characterized by aggressive local bone destruction, rapid progression, and a high tendency for pulmonary metastasis. Standard clinical management typically involves neoadjuvant chemotherapy followed by surgical resection and postoperative chemotherapy. Although the 5-year survival rate for patients with localized disease has improved considerably, outcomes remain poor for individuals with metastatic or recurrent osteosarcoma.

Current treatment strategies rely mainly on multi-agent chemotherapy combined with limb-salvage surgery or amputation, while targeted therapies and immunotherapies are being actively explored in clinical research. However, therapeutic progress has been limited by the highly heterogeneous genetic landscape of osteosarcoma, complex mechanisms driving tumor progression and metastasis, frequent chemoresistance, and the lack of predictive preclinical models that faithfully recapitulate human disease. Consequently, robust in vivo models are essential for investigating metastatic mechanisms, evaluating novel therapeutics, and supporting translational osteosarcoma research.

Why Zebrafish?

• Transparent larvae: Enable direct visualization of tumor growth and dissemination.
• Rapid engraftment: Human osteosarcoma cells rapidly engraft and proliferate in vivo.
• Conserved signaling: Conserved tumor signaling pathways support translational cancer studies.
• Scalable screening: Suitable for medium- to high-throughput drug efficacy screening.

Available Zebrafish Disease Models

Several validated zebrafish osteosarcoma models have been established for investigating tumor progression, metastatic dissemination, angiogenesis, and therapeutic response. The following models are among the most widely adopted in preclinical research.

Phenotypic Evaluation

Key Applications

• Pulmonary Metastasis Research: Investigate molecular mechanisms governing osteosarcoma dissemination and metastatic colonization.
• Anti-metastatic Drug Evaluation: Assess candidate therapeutics that inhibit tumor invasion and metastatic progression.
• Tumor Angiogenesis Studies: Evaluate interactions between osteosarcoma cells and host vasculature during tumor progression.
• Chemotherapy Resistance Research: Study resistance mechanisms to conventional chemotherapeutic agents, including doxorubicin, cisplatin, and methotrexate.
• Personalized Drug Sensitivity Testing: Support individualized therapeutic evaluation using patient-derived zebrafish xenograft models.

Study Examples

A zebrafish xenograft model was established by transplanting fluorescently labeled human U2OS osteosarcoma cells into zebrafish larvae to evaluate the in vivo antitumor activity of theabrownin (TB).

Fig. 1. Effect of TB on U2OS‐xenotransplanted larval zebrafish and normal zebrafish (Jin W, et al., 2018).

Reference

1. Jin W, Zhou L, et al. Theabrownin triggers DNA damage to suppress human osteosarcoma U2OS cells by activating p53 signalling pathway. Journal of Cellular and Molecular Medicine. 2018;22(9):4423–4436.