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Updated: Apr 23, 2026
Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
Modeling of human uveal melanoma in zebrafish xenograft embryos
Wietske van der Ent1, Claudia Burrello2, Amina F A S Teunisse3
1Institute of Biology, Leiden University, Leiden, The Netherlands Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
Purpose:
Uveal melanoma (UM) is fatal in up to 50% of patients because of liver metastases that are refractory to therapies currently available. While murine xenograft models for human uveal melanoma are available, they have limited utility for screening large compound libraries in drug discovery studies. Therefore, new robust preclinical models are needed that can efficiently evaluate drug efficacy for treatment of this malignancy.
Methods:
Uveal melanoma cell lines generated from primary tumors (92.1, Mel270) and metastases (OMM2.3, OMM2.5, OMM1) were injected into the yolk of 2-day-old zebrafish embryos. After 6 days, proliferation and active migration was quantified via automated confocal image analysis. To determine the suitability of this xenotransplantation model for drug testing, drugs with three different activities (dasatinib, quisinostat, and MLN-4924) were added to the water of uveal melanoma-engrafted embryos.
Results:
All tested UM cell lines proliferated and migrated in the embryos; significant differences could be discerned between cell lines: Cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors, and provided preclinical models for drug testing. Addition of the Src-inhibitor dasatinib in the water of engrafted embryos reduced proliferation and migration of high Src-expressing 92.1 cells, but did not affect low Src-expressing metastatic OMM2.3 cells. Two experimental anticancer drugs, quisinostat (a histone deacetylase inhibitor) and MLN-4924 (neddylation pathway inhibitor), blocked migration and proliferation of 92.1 and OMM2.3.
Conclusions:
We established a zebrafish xenograft model of human uveal melanoma with demonstrated applicability for screening large libraries of compounds in drug discovery studies.
Insights
A new zebrafish xenograft model effectively screens uveal melanoma drug efficacy. This model allows for rapid evaluation of potential treatments for uveal melanoma liver metastases, addressing limitations of current preclinical models.
Area of Science:
- Oncology
- Zebrafish models
- Drug discovery
Background:
- Uveal melanoma (UM) frequently metastasizes to the liver, leading to fatal outcomes in up to 50% of patients.
- Current therapies for uveal melanoma liver metastases are largely ineffective.
- Existing murine xenograft models have limitations for high-throughput drug screening.
Purpose of the Study:
- To establish and validate a robust zebrafish xenograft model for human uveal melanoma.
- To assess the utility of this model for preclinical drug screening and efficacy evaluation.
- To identify potential therapeutic agents for uveal melanoma treatment.
Main Methods:
- Human uveal melanoma cell lines (primary and metastatic) were xenotransplanted into zebrafish embryos.
- Embryo engraftment and subsequent cell proliferation and migration were quantified using automated confocal imaging.
- The efficacy of known drugs (dasatinib, quisinostat, MLN-4924) was tested by adding them to the water of engrafted zebrafish.
Main Results:
- All tested uveal melanoma cell lines exhibited proliferation and migration in zebrafish embryos.
- Metastatic cell lines demonstrated increased proliferation and migration compared to primary tumor cell lines.
- Dasatinib, quisinostat, and MLN-4924 demonstrated varying degrees of inhibition on uveal melanoma cell proliferation and migration in the model.
Conclusions:
- A zebrafish xenograft model for human uveal melanoma has been successfully established.
- This model is suitable for screening large compound libraries for drug discovery.
- The model shows promise for evaluating drug efficacy against uveal melanoma liver metastases.
