Zebrafish embryo as a tool to study tumor/endothelial cell cross-talk

Abstract

Tumor/endothelial cell cross-talk plays a pivotal role in the growth, neovascularization and metastatic dissemination of human cancer. Recent observations have shown that the teleost zebrafish (Danio rerio) may represent a powerful experimental platform in cancer research. Various tumor models have been established in zebrafish adults, juveniles, and embryos and novel genetic tools and high resolution in vivo imaging techniques have been exploited. In particular, grafting of mammalian tumor cells in zebrafish embryo body may simulate early stages of tumor development, neovascularization, and local invasion whereas the injection of cancer cells in the bloodstream of zebrafish embryo may allow the study of metastatic homing and colonization. This review focuses on the recent advances in tumor xenotransplantation in zebrafish embryo for the in vivo study of the cancer neovascularization, invasion and metastatic processes. This article is part of a Special Issue entitled: Animal Models of Disease.

The broad-spectrum anti-DNA virus agent cidofovir inhibits lung metastasis of virus-independent, FGF2-driven tumors

“…FGF2-dependent B16-F10 melanoma cells represent a prototypic model of experimental metastasis following their injection in the bloodstream of mice [36,37] or zebrafish embryos [38]. On this basis, given the prominent role of FGF2 in tumor progression and metastatic activity of these cells [26 and references therein], we investigated whether the anti-metastatic potential of CDV could be extended also to these virus-independent tumor cells.…”

“…B16-F10 melanoma cells stably transfected with DsRed fluorescent protein (DsRed-B16-F10 cells) were injected in the blood circulation in the ventral region of the duct of Cuvier of zebrafish embryos (80-100 cells/embryo) at 48 h post-fertilization (hpf). After 24 h, embryos were transferred in fish water in the absence or in the presence of 100 μg/ml of CDV and the growth of tail micrometastases was followed under a fluorescence stereo microscope and quantified 5 days after cell injection by computerized image analysis of the embryo tails as described [38]. After cell injection, embryos were maintained at 33°C throughout the whole experimental period.…”

The Study of Glioma by Xenotransplantation in Zebrafish Early Life Stages

“…2008), making older life stages less suitable for in vivo imaging. Xenotransplantation of cancer cells into juvenile fish requires immunosuppression of the recipient fish through the delivery of dexamethasone (Eden et al 2014;Stoletov and Klemke 2008;Tobia et al 2013) or radiation (Taylor and Zon 2009;Zhang et al 2014). However, this is not necessarily a disadvantage, as GBM patients are often exposed to these treatments as well.…”

Zebrafish as an innovative model for neuroendocrine tumors

“…These questions and a better knowledge of the mechanisms and regulation of tumor angiogenesis in NETs may be clinically highly relevant to determine the best antiangiogenic therapeutic strategy. zebrafish (Tobia et al 2013), and the process of angiogenesis is mechanistically similar in embryonic and tumor development, we decided to perform the xenotransplantation of human NET cancer cells into the subperidermal space of zebrafish embryos (Fig. 1).…”

“…However, there are several disadvantages of using this model (Tobia et al 2011(Tobia et al , 2013, that need to be considered, such as: -Species-specific microenvironmental differences may affect the behavior of grafted mammalian tumor cells and the lack of some mammalian organs in fishes (such as mammary gland, prostate, and lung) precludes the possibility to perform orthotopic transplantation experiments and to investigate tissue-specific mechanisms of tumor cell homing and colonization in these organs. -Drug metabolism in zebrafish may be different from that in mammals.…”