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An orthotopic glioblastoma animal model suitable for high-throughput screenings
Karolinska Inst, Dept Med Biochem & Biophys, Div Translat Med & Chem Biol, Sci Life Lab, Stockholm, Sweden..
KTH, School of Engineering Sciences (SCI), Applied Physics, Biophysics. Royal Inst Technol, Sci Life Lab, Dept Appl Phys, Stockholm, Sweden..
Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, Stockholm, Sweden..
Karolinska Inst, Div Vasc Biol, Dept Med Biochem & Biophys, Stockholm, Sweden..
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2018 (English)In: Neuro-Oncology, ISSN 1522-8517, E-ISSN 1523-5866, Vol. 20, no 11, p. 1475-1484Article in journal (Refereed) Published
Abstract [en]

Background. Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens. Methods. We transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy. Results. We found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease. Conclusion. We have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to currently available orthotopic zebrafish models, our approach does not require technically challenging intracranial transplantation of single embryos. Our improved zebrafish model enables transplantation of thousands of embryos per hour, thus providing an orthotopic vertebrate GBM model for direct application in drug discovery screens.

Place, publisher, year, edition, pages
Oxford University Press, 2018. Vol. 20, no 11, p. 1475-1484
Keywords [en]
animal model, brain cancer, glioblastoma, orthotopic transplantation, zebrafish
National Category
Medical Biotechnology
Identifiers
URN: urn:nbn:se:kth:diva-239082DOI: 10.1093/neuonc/noy071ISI: 000448665500007PubMedID: 29750281Scopus ID: 2-s2.0-8505477168OAI: oai:DiVA.org:kth-239082DiVA, id: diva2:1264913
Funder
Torsten Söderbergs stiftelseGöran Gustafsson Foundation for Research in Natural Sciences and MedicineSwedish Research Council, 03950Swedish Research Council, 2015-00162Swedish Foundation for Strategic Research , RB13-0224Knut and Alice Wallenberg Foundation, KAW2014.273Swedish Cancer Society
Note

QC 20181121

Available from: 2018-11-21 Created: 2018-11-21 Last updated: 2018-11-21Bibliographically approved

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Edwards, Steven

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