ZFTool: A Software for Automatic Quantification of Cancer Cell Mass Evolution in Zebrafish

Background: Zebrafish (Danio rerio) is a model organism emerged for the study of human cancer. Compared with the murine model, the zebrafish model has several properties ideal for personalized therapies. The transparency of the zebrafish embryos and the development of the pigment-deficient “casper” zebrafish line give the capacity to directly observe cancer formation and progression in the living animal. Automatic quantification of cellular proliferation in vivo is critical to the development of personalized medicine. Methods: A new methodology was defined to automatically quantify the cancer cellular evolution. ZFTool was developed to establish a base threshold that eliminates the embryo auto-fluorescence and automatically measures the area and intensity of GFP (green-fluorescent protein) marked cells and define a proliferation index. Results: Proliferation index automatically computed on different targets demonstrates the efficiency of ZFTool to provide a good automatic quantification of cancer cell evolution and dissemination. Conclusion: Our results demonstrate that ZFTool is a reliable tool for the automatic quantification of the proliferation index, being a measure of cancer mass evolution in zebrafish eliminating the influence of its autofluorescence.

[1]  Shuning He,et al.  Transforming growth factor-β signalling controls human breast cancer metastasis in a zebrafish xenograft model , 2013, Breast Cancer Research.

[2]  Xiayang Xie,et al.  Evaluating human cancer cell metastasis in zebrafish , 2013, BMC Cancer.

[3]  Raphaël Marée,et al.  Automated processing of zebrafish imaging data: a survey. , 2013, Zebrafish.

[4]  N. Trede,et al.  The zebrafish as a model for cancer , 2010, Disease Models & Mechanisms.

[5]  Marissa A. LeBlanc,et al.  Focused chemical genomics using zebrafish xenotransplantation as a pre-clinical therapeutic platform for T-cell acute lymphoblastic leukemia , 2015, Haematologica.

[6]  M. J. Carreira,et al.  Improving zebrafish embryo xenotransplantation conditions by increasing incubation temperature and establishing a proliferation index with ZFtool , 2018, BMC Cancer.

[7]  H. Spaink,et al.  Automated Whole Animal Bio-Imaging Assay for Human Cancer Dissemination , 2012, PloS one.

[8]  G. Dellaire,et al.  Hooking the big one: the potential of zebrafish xenotransplantation to reform cancer drug screening in the genomic era , 2014, Disease Models & Mechanisms.

[9]  Shaukat Ali,et al.  Zebrafish embryos and larvae: a new generation of disease models and drug screens. , 2011, Birth defects research. Part C, Embryo today : reviews.

[10]  Seok-Yong Choi,et al.  A novel zebrafish human tumor xenograft model validated for anti-cancer drug screening. , 2012, Molecular bioSystems.

[11]  M. Konantz,et al.  Zebrafish xenografts as a tool for in vivo studies on human cancer , 2012, Annals of the New York Academy of Sciences.

[12]  Jeroen Bakkers,et al.  Zebrafish as a model to study cardiac development and human cardiac disease , 2011, Cardiovascular research.

[13]  Oliver Bandmann,et al.  Zebrafish as a new animal model for movement disorders , 2008, Journal of neurochemistry.

[14]  Olli Yli-Harja,et al.  ZebIAT, an image analysis tool for registering zebrafish embryos and quantifying cancer metastasis , 2013, BMC Bioinformatics.