Ann. N.Y. Acad. Sci. ISSN 0077-8923 ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Issue: Hematopoietic Stem Cells VIII Zebraﬁsh xenografts as a tool for in vivo studies on human cancer Martina Konantz, 1 Tugce B. Balci, 2 Udo F. Hartwig, 3 Graham Dellaire, 4,5 Maya C. Andr´ e, 6,7 Jason N. Berman, 2,5,8,9 and Claudia Lengerke 1 1 Department of Hematology and Oncology, University of T¨ ubingen Medical Center II, T ¨ ubingen, Germany. 2 IWK Health Centre, Halifax, Nova Scotia, Canada. 3 3rd Department of Medicine—Hematology, Oncology and Pneumology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany. 4 Departments of Biochemistry and Molecular Biology, Dalhousie University, Halifax, Nova Scotia, Canada. 5 Department of Pathology, Dalhousie University, Halifax, Nova Scotia, Canada. 6 Department of Pediatric Hematology/Oncology, University Children’s Hospital, Eberhard Karls University, T¨ ubingen, Germany. 7 Department of Pediatric Intensive Care Medicine, University Children’s Hospital (UKBB), Basel, Switzerland. 8 Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada. 9 Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada Address for correspondence: Claudia Lengerke, M.D., University of T¨ ubingen Medical Center II, Otfried-Mueller-Strasse 10, 72076 T ¨ ubingen, Germany. claudia.lengerke@med.uni-tuebingen.de The zebraﬁsh has become a powerful vertebrate model for genetic studies of embryonic development and organogen- esis 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 xenotrans- plantation of human cells into zebraﬁsh, highlighting the advantages and limitations of this model in comparison to classical murine models of xenotransplantation. Keywords: human xenografts; zebraﬁsh; organogenesis; cancer biology; xenotransplantation Introduction Over the past decades, the zebraﬁsh has developed into a powerful vertebrate model for genetic stud- ies of embryonic development and organogenesis. The high fecundity and short generation times of the zebraﬁsh embryo facilitate the generation of transgenic lines and allow performance of large- scale mutagenesis screens that can identify novel genetic pathways. 1–6 Transient genetic modiﬁca- tion can be readily achieved in the early embryo via direct microinjection of messenger ribonu- cleic acid (mRNA) to obtain gene overexpres- sion or morpholino oligonucleotides, inducing gene knockdown through antisense technology. Impor- tantly, high interspecies conservation of molecular pathways has been shown between zebraﬁsh and mammals. 7,8 In addition to developmental studies, zebraﬁsh have increasingly been employed to analyze cancer and genetic diseases through diverse forward and re- verse genetic approaches. Chemical carcinogenesis screens providing cancer models resembling human disease and transgenic zebraﬁsh expressing human and mouse oncogenes and tumor suppressors have enabled studies on tumor formation and mainte- nance in zebraﬁsh. 9–15 Despite general conservation of oncogenic pathways between zebraﬁsh and hu- mans, exceptions exist, such as the apparent ab- sence of the INK4a/ARF tumor suppressor gene in zebraﬁsh. 16 Thus, full recapitulation of the genetic complexity of human tumors may not be possible doi: 10.1111/j.1749-6632.2012.06575.x 124 Ann. N.Y. Acad. Sci. 1266 (2012) 124–137 c  2012 New York Academy of Sciences.