Embryonic Zebrafish: Different Phenotypes after Injection of Human Uveal Melanoma Cells

Ent, Wietske van der; Burrello, Claudia; Lange, Mark; Velden, Pieter A. van der; Jochemsen, Aart G.; Jager, Martine J.; Snaar-Jagalska, B. Ewa

doi:10.1159/000370159

Cited by 28 publications

(21 citation statements)

References 32 publications

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“…3). Interestingly, this phenomenon has also been seen in the zebrafish model [26]. Histological and immunohistochemical examination of the chick liver demonstrated the presence of micro-metastatic foci of both cell lines in this organ (fig.…”

Section: The Chick Embryo Model In Cancer Biologymentioning

confidence: 59%

Use of the Chick Embryo Model in Uveal Melanoma

et al. 2015

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Animal models play a crucial role in basic and translational oncology research. Conventional rodent experiments, however, face ethical, practical and technical issues that limit their use. The chick embryo represents an accessible and economical in vivo model, which has long been used in developmental biology and for the study of angiogenesis. It is also a recognised xenograft model, and because of its lack of immune system in early development, the chick embryo has established itself as a key model system for cancer research, with which to study various steps in the metastatic process. In this chapter, we review the chick embryo model and the technical approaches adopted by cancer biologists, including advances in real-time imaging, and discuss how this has been or can be applied to improve our understanding of the biological events during uveal melanoma development and metastasis.

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Section: The Chick Embryo Model In Cancer Biologymentioning

confidence: 59%

Use of the Chick Embryo Model in Uveal Melanoma

et al. 2015

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“…However, metastatic cutaneous human melanoma did not migrate to the eyes when injected into zebrafish embryos. 30,41 In a recent study, 42 primary and metastatic uveal melanoma cells were seen to migrate to the eye in 10% of the embryos. This suggests that the migration of eye cancer cells to the eye is not mutation dependent, but controlled by others factors, which should be evaluated in the future.…”

Section: Discussionmentioning

confidence: 96%

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

Pontes

Groenewoud

Cao

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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Citation: Pontes KCS, Groenewoud A, Cao J, Ataide LMS, Snaar-Jagalska E, Jager MJ. Evaluation of (fli:GFP) Casper zebrafish embryos as a model for human conjunctival melanoma. Invest Ophthalmol Vis Sci. 2017;58:6065-6071. DOI:10.1167/iovs.17-22023 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.

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“…This model was suitable to test the efficacy of different experimental anticancer drugs (e.g., quisinostat and the neddylation [ubiquitin-like protein NEDD8 conjugation to target proteins] pathway inhibitor MLN-4924) which repressed the migration and proliferation of UM cells. As the drugs were dissolved in the water, the rate of drug absorbance into zebrafish embryos needs a better characterization [390]. …”

Section: Animal Modelsmentioning

confidence: 99%

The biology of uveal melanoma

Amaro

Gangemi

Piaggio

et al. 2017

Cancer Metastasis Rev

191

193

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Uveal melanoma (UM), a rare cancer of the eye, is distinct from cutaneous melanoma by its etiology, the mutation frequency and profile, and its clinical behavior including resistance to targeted therapy and immune checkpoint blockers. Primary disease is efficiently controlled by surgery or radiation therapy, but about half of UMs develop distant metastasis mostly to the liver. Survival of patients with metastasis is below 1 year and has not improved in decades. Recent years have brought a deep understanding of UM biology characterized by initiating mutations in the G proteins GNAQ and GNA11. Cytogenetic alterations, in particular monosomy of chromosome 3 and amplification of the long arm of chromosome 8, and mutation of the BRCA1-associated protein 1, BAP1, a tumor suppressor gene, or the splicing factor SF3B1 determine UM metastasis. Cytogenetic and molecular profiling allow for a very precise prognostication that is still not matched by efficacious adjuvant therapies. G protein signaling has been shown to activate the YAP/TAZ pathway independent of HIPPO, and conventional signaling via the mitogen-activated kinase pathway probably also contributes to UM development and progression. Several lines of evidence indicate that inflammation and macrophages play a pro-tumor role in UM and in its hepatic metastases. UM cells benefit from the immune privilege in the eye and may adopt several mechanisms involved in this privilege for tumor escape that act even after leaving the niche. Here, we review the current knowledge of the biology of UM and discuss recent approaches to UM treatment.

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Embryonic Zebrafish: Different Phenotypes after Injection of Human Uveal Melanoma Cells

Cited by 28 publications

References 32 publications

Use of the Chick Embryo Model in Uveal Melanoma

Use of the Chick Embryo Model in Uveal Melanoma

Evaluation of (fli:GFP) Casper Zebrafish Embryos as a Model for Human Conjunctival Melanoma

The biology of uveal melanoma

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