Zebrafish as an innovative model for neuroendocrine tumors

Tumor models have a relevant role in furthering our understanding of the biology of malignant disease and in preclinical cancer research. Only few models are available for neuroendocrine tumors (NETs), probably due to the rarity and heterogeneity of this group of neoplasms. This review provides insights into the current state of the art of zebrafish as a model in cancer research, focusing on potential applications in NETs. Zebrafish has a complex circulatory system similar to that of mammals. A novel angiogenesis assay based on the injection of human neuroendocrine tumor cell lines (TT and DMS79 cells) into the subperidermal space of the zebrafish embryos has been developed. Proangiogenic factors locally released by the tumor graft affect the normal developmental pattern of the subintestinal vessels (SIV) by stimulating the migration and growth of sprouting vessels towards the implant. In addition, a description of the striking homology between zebrafish and humans of molecular targets involved in tumor angiogenesis (somatostatin receptors, dopamine receptors, mTOR), and currently used as targeted therapy of NETs, is reported.