title: Patient-derived xenograft in zebrafish embryos: a new platform for translational research in neuroendocrine tumors.
abstract: Preclinical research on neuroendocrine tumors usually involves immortalized cell lines and few animal models. In the present study we described an in vivo model based on patient-derived xenografts of neuroendocrine tumor cells in zebrafish (Danio rerio) embryos, allowing a rapid analysis of the angiogenic and invasive potential. Patient-derived neuroendocrine tumor cells were transplanted in 48 hours post-fertilization Tg(fli1a:EGFP)y1zebrafish embryos that express enhanced green fluorescent protein in the entire vasculature. Neuroendocrine tumor cells, stained with CM-Dil, were injected into the subperidermal (perivitelline) space, close to the developing subintestinal venous plexus. A proper control group, represented by zebrafish injected with only D-PBS, was included in this study. Angiogenic and invasive potentials of each patient-derived xenograft were evaluated by both epifluorescence and confocal microscopes. Six out of eight neuroendocrine tumor samples were successfully transplanted in zebrafish embryos. Although the implanted tumor mass had a limited size (about 100 cells for embryos), patient-derived xenografts showed pro-angiogenic (5 cases) and invasive (6 cases) behaviors within 48 hours post injection. Patient-derived xenograft in zebrafish embryos appears to be a reliable in vivo preclinical model for neuroendocrine tumors, tumors with often limited cell availability. The rapidity of this procedure makes our model a promising platform to perform preclinical drug screening and opens a new scenario for personalized treatment in patients with neuroendocrine tumors.
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: Germano
authors.initials: G
authors.lastname: Gaudenzi
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Albertelli
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Dicitore
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Würth
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Gatto
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Barbieri
authors.affiliation: Department of Biosciences, University of Milan, Milan, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Cotelli
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
authors.forename: Tullio
authors.initials: T
authors.lastname: Florio
authors.affiliation: Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST Genova, Genova, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Ferone
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.|Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Persani
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.|Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: Giovanni
authors.identifier: http://orcid.org/0000-0003-2478-683X
authors.initials: G
authors.lastname: Vitale
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D004353:Drug Evaluation, Preclinical; D005260:Female; D064593:Heterografts / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009368:Neoplasm Transplantation / Q000379:methods*; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000473:pathology*; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology*; D061251:Primary Cell Culture; D057170:Translational Research, Biomedical / Q000379:methods*; D015027:Zebrafish / Q000502:physiology*
keywords: Angiogenesis; Neuroendocrine tumors; Patient-derived xenografts; Zebrafish