The Study of Glioma by Xenotransplantation in Zebrafish Early Life Stages

Abstract

SummaryZebrafish (Danio rerio) and their transparent embryos are becoming an increasingly popular tool for studying processes involved in tumor progression and in the search for novel tumor treatment approaches. The xenotransplantation of fluorescently labeled mammalian cancer cells into zebrafish embryos is an approach enabling relatively high-throughput in vivo analyses. The small size of the embryos as well as the relative simplicity of their manipulation and maintenance allow for large numbers of embryos to be processed efficiently in a short time and at low cost. Furthermore, the possibility of fluorescence microscopic imaging of tumor progression within zebrafish embryos and larvae holds unprecedented potential for the real-time visualization of these processes in vivo. This review presents the methodologies of xenotransplantation studies on zebrafish involving research on tumor invasion, proliferation, tumor-induced angiogenesis and screening for antitumor therapeutics. We further focus on the application of these zebrafish to the study of glioma; in particular, its most common and malignant form, glioblastoma. (J Histochem Cytochem 63:749-761, 2015)

Standardized orthotopic xenografts in zebrafish reveal glioma cell line specific characteristics and tumor cell heterogeneity

“…More recently, zebrafish have been exploited to analyze tumor development and for chemical screens ( Peal et al, 2010 ; Lally et al, 2007 ), leading to the identification of several candidate therapeutics for melanoma and leukemia that are currently being evaluated in patients (NCT02354417, NCT01611675 and NCT01512251; White et al, 2013 ; Konantz et al, 2012 ). Glioma cells have previously been transplanted into zebrafish ( Vittori et al, 2015 ). In several studies, serum-grown adherent glioma cell lines were transplanted into the yolk to analyze angiogenesis and tumor growth and showed that these cells formed tumors on the yolk, promoted angiogenesis and were responsive to therapeutics ( Geiger et al, 2008 ; Zhao et al, 2009 ; Lally et al, 2007 ; Yang et al, 2013 ).…”

Glioma: experimental models and reality

“…A potentially interesting example is the zebrafish ( Danio rerio ) model for the study of gliomas [154, 158]. Zebrafish embryos are increasingly used for cancer studies since the discovery that pathways of tumorigenesis are similar in humans and zebrafish [66].…”

RECQ1 Helicase Silencing Decreases the Tumour Growth Rate of U87 Glioblastoma Cell Xenografts in Zebrafish Embryos

“…Zebrafish are an emerging model in glioma research [ 10 , 11 ], and xenotransplantation of human glioblastoma has proven to be a successful approach. In previous studies, fluorescently labelled or fluorescent protein-expressing glioblastoma cells were implanted in zebrafish, in order to observe tumour-associated angiogenesis, to determine the effects of drugs, and to study the involvement of signalling pathways, such as Wnt signalling, in tumour progression [ 12 , 13 , 14 , 15 ].…”

“…One of the benefits of this model is that zebrafish embryos lack an adaptive immune system, obviating the need for immunosuppression [ 16 ]. Another advantage is the transparency of the embryos, which makes imaging of tumour progression at single cell resolution easier than in mammalian models [ 10 , 13 , 17 ]. Furthermore, the fecundity of zebrafish, and the low cost of maintenance and experimentation, are advantages of the zebrafish model, that holds great promise for its use in drug screening in vivo [ 18 , 19 , 20 ].…”