PUBLICATION
Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma
- Authors
- Pontes, K.C.S., Groenewoud, A., Cao, J., Ataide, L.M.S., Snaar-Jagalska, E., Jager, M.J.
- ID
- ZDB-PUB-171206-10
- Date
- 2017
- Source
- Investigative ophthalmology & visual science 58: 6065-6071 (Journal)
- Registered Authors
- Snaar-Jagalska, Ewa B.
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- CASP8 and FADD-Like Apoptosis Regulating Protein/genetics*
- CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism
- Cell Line, Tumor
- Cell Movement
- Cell Proliferation
- Conjunctival Neoplasms/embryology
- Conjunctival Neoplasms/genetics*
- Conjunctival Neoplasms/metabolism
- DNA Mutational Analysis
- DNA, Neoplasm/genetics*
- Humans
- Immunohistochemistry
- Melanoma/embryology
- Melanoma/genetics*
- Melanoma/metabolism
- Mutation*
- Neoplasms, Experimental
- Zebrafish/embryology
- PubMed
- 29204645 Full text @ Invest. Ophthalmol. Vis. Sci.
Citation
Pontes, K.C.S., Groenewoud, A., Cao, J., Ataide, L.M.S., Snaar-Jagalska, E., Jager, M.J. (2017) Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma. Investigative ophthalmology & visual science. 58:6065-6071.
Abstract
Purpose Conjunctival melanoma (CM) is a rare malignant disease that can lead to recurrences and metastases. There is a lack of effective treatments for the metastases, and we set out to develop a new animal model to test potential therapies. Zebrafish are being used as a model for many diseases, and our goal was to test whether this animal could be used to study CM.
Methods Three human CM cell lines (CRMM-1 and CM2005.1, which both harbor a B-RAF mutation, and CRMM-2, which has an N-RAS mutation) were injected into the yolk sac, around the eye, and into the duct of Cuvier of transgenic (fli:GFP) Casper zebrafish embryos. Fluorescent and confocal images were taken to assess the phenotype and the behavior of engrafted cells and to test the effect of Vemurafenib as a treatment against CM.
Results While the cells that had been injected inside the yolk sac died and those injected around the eye sporadically went into the circulation, the cells that had been injected into the duct of Cuvier colonized the zebrafish: cells from all three cell lines proliferated and disseminated to the eyes, where they formed clusters, and to the tail, where we noticed extravasation and micrometastases. Vemurafenib, a potent agent for treatment of B-RAF V600E-positive melanoma, inhibited outgrowth of CRMM-1 and CM2005.1 cells in a mutation-dependent way.
Conclusions The (fli:GFP) Casper zebrafish embryo can be used as an efficient animal model to study metastatic behavior of human CM cells and warrants further testing of drug efficacy to aid care of CM patients.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping