Zebrafish xenografts as a tool for in vivo studies on human cancer

Abstract

The zebrafish has become a powerful vertebrate model for genetic studies of embryonic development and organogenesis and increasingly for studies in cancer biology. Zebrafish facilitate the performance of reverse and forward genetic approaches, including mutagenesis and small molecule screens. Moreover, several studies report the feasibility of xenotransplanting human cells into zebrafish embryos and adult fish. This model provides a unique opportunity to monitor tumor-induced angiogenesis, invasiveness, and response to a range of treatments in vivo and in real time. Despite the high conservation of gene function between fish and humans, concern remains that potential differences in zebrafish tissue niches and/or missing microenvironmental cues could limit the relevance and translational utility of data obtained from zebrafish human cancer cell xenograft models. Here, we summarize current data on xenotransplantation of human cells into zebrafish, highlighting the advantages and limitations of this model in comparison to classical murine models of xenotransplantation.

A Protocol for Genetic Induction and Visualization of Benign and Invasive Tumors in Cephalic Complexes of <em>Drosophila melanogaster</em>

“…The simple protocol presented here makes it possible to genetically induce benign and invasive tumors in a whole organism and then study the biology associated with the progression of tumors in this model. Most of the existing techniques in Drosophila and other organisms either utilize a cell culture based system to understand tumorigenesis & metastasis or a system that employs transplantation of primary tumor tissues into adult hosts [23][24][25][26][27] . Both the cell based and transplantation techniques have their limitations.…”

“…Using mutagenesis and overexpression tools we have arrived at a better understanding of various oncogenes and tumor suppressor genes [18][19][20][21][22] . However, tumor metastasis is a result of cooperation between several genetic lesions that has been studied primarily in cell culture models 23,24 as well as various xenograft models [25][26][27] . These models though powerful have their limitations as they do not mimic entirely the conditions found in a living organism.…”

Zebrafish as an innovative model for neuroendocrine tumors

“…Although there are evident structural and physiological differences between zebrafish and humans, the zebrafish provides several advantages when compared with other vertebrate model systems (Lieschke & Currie 2007, Fieramonti et al 2012, Konantz et al 2012, Santoriello & Zon 2012.…”

“…Although murine xenotransplant model remains the gold standard for studies in the field of human cancer research and drug development, there are several limitations associated with this model: long duration of time required to have a visible tumor implant and to perform experiments (from several weeks to months); requirement of a skilled technician for the complexity of several procedures; immunosuppressed mice are required to avoid transplant rejection, these animals are more susceptible to infection and drug toxicity than normal mice and need specific housing and care; its laborious and time-consuming process makes this model very expensive; large number of cells (about 1 million) are required to generate a tumor, making it less suitable as a xenotransplant model using primary tumor cells; high difficulties to generate mouse xenotransplant models able to metastasize (Haldi et al 2006, Konantz et al 2012.…”

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

“…The teleost zebrafish (Dario rerio) has been used as a model organism for development study since the 1960s and was first applied to the study of tumor pathogenesis in 1982 [9][10][11] . Ease of maintenance, small body size, and high fecundity make the zebrafish a robust model for large-scale forward genetic screens to identify mutations that confer abnormal and pathological phenotypes 10 .…”