Related Experiment Video
Updated: Aug 1, 2025
Ortho- and Ectopic Zebrafish Xeno-Engraftment of Ocular Melanoma to Recapitulate Primary Tumor and Experimental Metastasis Development
Published on: September 4, 2021
Zebrafish Patient-Derived Xenograft Model as a Preclinical Platform for Uveal Melanoma Drug Discovery
Jie Yin1, Gangyin Zhao1, Helen Kalirai2
1Institute of Biology, Leiden University, 2333 BE Leiden, The Netherlands.
Abstract:
Uveal melanoma (UM) is a rare malignant cancer of the eye, with up to 50% of patients dying from metastasis, for which no effective treatment is available. Due to the rarity of the disease, there is a great need to harness the limited material available from primary tumors and metastases for advanced research and preclinical drug screening. We established a platform to isolate, preserve, and transiently recover viable tissues, followed by the generation of spheroid cultures derived from primary UM. All assessed tumor-derived samples formed spheroids in culture within 24 h and stained positive for melanocyte-specific markers, indicating the retention of their melanocytic origin. These short-lived spheroids were only maintained for the duration of the experiment (7 days) or re-established from frozen tumor tissue acquired from the same patient. Intravenous injection of fluorescently labeled UM cells derived from these spheroids into zebrafish yielded a reproducible metastatic phenotype and recapitulated molecular features of the disseminating UM. This approach allowed for the experimental replications required for reliable drug screening (at least 2 individual biological experiments, with n > 20). Drug treatments with navitoclax and everolimus validated the zebrafish patient-derived model as a versatile preclinical tool for screening anti-UM drugs and as a preclinical platform to predict personalized drug responses.
Insights
Researchers developed a new platform using patient tumor samples to create eye cancer (uveal melanoma) spheroids. This model effectively replicates metastasis in zebrafish, enabling reliable preclinical drug screening and personalized treatment prediction.
Area of Science:
- Ophthalmology
- Oncology
- Translational Research
Background:
- Uveal melanoma (UM) is a rare eye cancer with a high mortality rate due to metastasis, lacking effective treatments.
- Limited patient tumor samples necessitate innovative methods for research and drug development.
- Existing models often fail to fully recapitulate UM's metastatic potential and molecular characteristics.
Purpose of the Study:
- To establish a platform for isolating, preserving, and culturing viable uveal melanoma tissues.
- To generate patient-derived spheroid cultures from primary UM for preclinical research.
- To validate a zebrafish model using these spheroids for studying UM metastasis and drug screening.
Main Methods:
- Development of a platform to isolate, preserve, and recover viable primary UM tissues.
- Generation of spheroid cultures from UM tissues, confirmed by melanocyte-specific markers.
- Xenotransplantation of UM spheroids into zebrafish to assess metastatic potential and drug response.
Main Results:
- Established spheroid cultures from all assessed UM samples, retaining melanocytic origin.
- Zebrafish model demonstrated reproducible metastatic phenotype and recapitulated UM molecular features.
- Navitoclax and everolimus treatments in the model showed potential for predicting drug responses.
Conclusions:
- The developed platform enables the creation of short-term, patient-derived UM spheroids.
- The zebrafish xenotransplantation model serves as a versatile tool for preclinical UM drug screening.
- This patient-derived model shows promise for predicting personalized drug responses in uveal melanoma.
