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

Abstract

Although murine xenograft models for human uveal melanoma (UM) are available, they are of limited utility for screening large compound libraries for the discovery of new drugs. We need new preclinical models which can efficiently evaluate drugs that can treat UM metastases. The zebrafish embryonic model is ideal for drug screening purposes because it allows the investigation of potential antitumor properties of drugs within 1 week. The optical transparency of the zebrafish provides unique possibilities for live imaging of fluorescence-labelled cancer cells and their behavior. In addition, the adaptive immune response, which is responsible for the rejection of transplanted material, is not yet present in the early stages of fish development, and systemic immunosuppression is therefore not required to allow growth of tumor cells. We studied the behavior of UM cells following injection into zebrafish embryos and observed different phenotypes. We also analyzed cell migration, proliferation, formation of micrometastasis and interaction with the host microenvironment. Significant differences were noted between cell lines: cells derived from metastases showed more migration and proliferation than cells derived from the primary tumors. The addition of the c-Met inhibitor crizotinib to the water in which the larvae were kept reduced the migration and proliferation of UM cells expressing c-Met. This indicates the applicability of the zebrafish xenografts for testing novel inhibitory compounds and provides a fast and sensitive in vivo vertebrate model for preclinical drug screening to combat UM.