Zebrafish Gastric Cancer Models

Introduction

Gastric cancer (GC) remains one of the most prevalent and lethal malignancies worldwide, characterized by high biological heterogeneity and a significant global health burden. Most cases are histologically classified as adenocarcinomas, often diagnosed at advanced stages due to asymptomatic early progression. Pathological hallmarks include uncontrolled mucosal cell proliferation, chronic inflammation, and frequent metastasis to the liver and peritoneum. While surgical resection and systemic chemotherapy (e.g., platinum-based regimens) are standard treatments, the clinical landscape has shifted toward targeted therapies (anti-HER2) and immunotherapies.

Despite these advancements, research is hindered by the complex tumor microenvironment and the high rate of chemoresistance. Traditional rodent models, while valuable, are often cost-prohibitive for large-scale screening and fail to capture the real-time dynamics of tumor-host interactions. Consequently, there is an urgent need for cost-effective, high-throughput models that can accurately predict clinical responses. Zebrafish models have emerged as a powerful solution, bridging the gap between in vitro assays and mammalian studies by providing a unique platform for phenotypic screening and personalized medicine.

Why Zebrafish?

• Gastrointestinal Homology: Conserved digestive anatomy and molecular signaling enable accurate modeling of human gastric oncogenesis.
• Real-time Visualization: Transparent larvae allow non-invasive monitoring of mucosal invasion and gastric tumor-induced angiogenesis.
• Fast-Track zPDX: Delivers personalized drug sensitivity profiles within days, matching the clinical urgency of gastric cancer.
• Scalable Screening: High-throughput capabilities facilitate rapid identification of compounds targeting gastric-specific chemoresistance.

Available Zebrafish Disease Models

We offer a comprehensive suite of gastric cancer models tailored to different research objectives:

Phenotypic Evaluation

Key Applications

• Lead Optimization: Assessing the in vivo efficacy and safety of small molecule libraries.
• Target Discovery: Validating the role of novel genes in gastric cancer progression using our CRISPR/Cas9 platform.
• Anti-Metastasis Screening: Identifying compounds that specifically block the invasive and migratory potential of GC cells.
• Angiogenesis Inhibition: Evaluating the potency of VEGFR inhibitors and other anti-angiogenic agents.
• Mechanism of Action (MoA) Studies: Utilizing our transgenic reporter lines to elucidate the cellular pathways targeted by candidate drugs.

Study Examples

Human gastric cancer cell lines AGS and SGC-7901, as well as primary gastric cancer cells from patient tumors, were fluorescently labeled and microinjected into the yolk sac of 48 hpf Tg(fli1:EGFP) zebrafish embryos. The model was used to monitor tumor cell proliferation, angiogenesis, invasion, and metastatic dissemination in vivo.

Fig. 1. Primary cells from GC tissue induced angiogenesis and metastasized in larval zebrafish (fli-eGFP) (Wu J, et al., 2017).

Reference

1. Wu, JQ., Zhai, J., et al. Patient-derived xenograft in zebrafish embryos: a new platform for translational research in gastric cancer. J Exp Clin Cancer Res 36, 160 (2017).