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Updated: Oct 9, 2025
Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation
Chiara Tobia1, Daniela Coltrini1, Roberto Ronca1
1Department of Molecular and Translational Medicine, University of Brescia, 25123 Brescia, Italy.
Abstract:
Uveal melanoma is a highly metastatic tumor, representing the most common primary intraocular malignancy in adults. Tumor cell xenografts in zebrafish embryos may provide the opportunity to study in vivo different aspects of the neoplastic disease and its response to therapy. Here, we established an orthotopic model of uveal melanoma in zebrafish by injecting highly metastatic murine B16-BL6 and B16-LS9 melanoma cells, human A375M melanoma cells, and human 92.1 uveal melanoma cells into the eye of zebrafish embryos in the proximity of the developing choroidal vasculature. Immunohistochemical and immunofluorescence analyses showed that melanoma cells proliferate during the first four days after injection and move towards the eye surface. Moreover, bioluminescence analysis of luciferase-expressing human 92.1 uveal melanoma cells allowed the quantitative assessment of the antitumor activity exerted by the canonical chemotherapeutic drugs paclitaxel, panobinostat, and everolimus after their injection into the grafted eye. Altogether, our data demonstrate that the zebrafish embryo eye is a permissive environment for the growth of invasive cutaneous and uveal melanoma cells. In addition, we have established a new luciferase-based in vivo orthotopic model that allows the quantification of human uveal melanoma cells engrafted in the zebrafish embryo eye, and which may represent a suitable tool for the screening of novel drug candidates for uveal melanoma therapy.
Insights
Researchers developed a zebrafish embryo eye model for studying uveal melanoma, a common eye cancer. This new model allows for the quantitative assessment of drug efficacy against uveal melanoma cells.
Area of Science:
- Ophthalmology
- Oncology
- Zebrafish Models
Background:
- Uveal melanoma is the most common primary intraocular malignancy in adults.
- It is a highly metastatic tumor with limited therapeutic options.
- Zebrafish embryo xenografts offer a potential in vivo model for studying cancer and therapy response.
Purpose of the Study:
- To establish an orthotopic xenograft model of uveal melanoma in zebrafish embryos.
- To evaluate the suitability of the zebrafish eye as a permissive environment for melanoma cell growth.
- To develop a luciferase-based model for quantitative assessment of therapeutic drug efficacy.
Main Methods:
- Injection of murine and human melanoma cell lines (B16-BL6, B16-LS9, A375M, 92.1) into the zebrafish embryo eye.
- Immunohistochemical and immunofluorescence analyses to track cell proliferation and migration.
- Bioluminescence imaging of luciferase-expressing 92.1 cells to quantify drug response.
Main Results:
- Melanoma cells successfully engrafted, proliferated, and migrated towards the eye surface within four days.
- The zebrafish embryo eye proved to be a permissive environment for both cutaneous and uveal melanoma cells.
- The luciferase-based model enabled quantitative assessment of paclitaxel, panobinostat, and everolimus efficacy.
Conclusions:
- The zebrafish embryo eye is a viable in vivo model for uveal melanoma research.
- A novel luciferase-based orthotopic model was established for quantifying human uveal melanoma cells in zebrafish.
- This model serves as a valuable tool for screening novel therapeutic drug candidates for uveal melanoma.
