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Patient-derived xenograft in zebrafish embryos: a new platform for translational research in neuroendocrine tumors

  • Endocrine Methods and Techniques
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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) y1 zebrafish 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.

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Acknowledgments

This work was partially supported by the Italian Ministry of Education, Research and University (FIRB RBAP11884M).

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Authors and Affiliations

  1. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy

    Germano Gaudenzi, Luca Persani & Giovanni Vitale

  2. Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy

    Manuela Albertelli, Roberto Würth, Federico Gatto, Federica Barbieri, Tullio Florio & Diego Ferone

  3. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, Milan, Italy

    Alessandra Dicitore, Luca Persani & Giovanni Vitale

  4. Department of Biosciences, University of Milan, Milan, Italy

    Franco Cotelli

  5. IRCCS AOU San Martino-IST Genova, Genova, Italy

    Diego Ferone

Authors
  1. Germano Gaudenzi
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  2. Manuela Albertelli
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  3. Alessandra Dicitore
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  4. Roberto Würth
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  5. Federico Gatto
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  6. Federica Barbieri
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  7. Franco Cotelli
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  8. Tullio Florio
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  9. Diego Ferone
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  10. Luca Persani
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  11. Giovanni Vitale
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The authors declare that they have no conflict of interest.

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Gaudenzi, G., Albertelli, M., Dicitore, A. et al. Patient-derived xenograft in zebrafish embryos: a new platform for translational research in neuroendocrine tumors. Endocrine 57, 214–219 (2017). https://doi.org/10.1007/s12020-016-1048-9

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  • DOI: https://doi.org/10.1007/s12020-016-1048-9

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