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In vivo animal models for studying brain metastasis: value and limitations

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Abstract

Brain metastasis is associated with a particular poor prognosis. Novel insight into the brain metastatic process is therefore warranted. Several preclinical models of brain tumor metastasis have been developed during the last 60 years, and they have in part revealed some of the mechanisms underlying the metastatic process. This review discusses mechanisms of brain metastasis with a key focus of the development of animal model systems. This includes the use of rodent, syngeneic brain metastasis models (spontaneous, chemically induced and genetically engineered models) and human xenotransplantation models (ectopic inoculation and orthotopic models). Current information indicates that none of these fully reflect tumor development seen in patients with metastatic disease. The various model systems used, however, have provided important insight into specific mechanisms of the metastatic process related to the brain. By combining the knowledge obtained from animal models, new important information on the molecular mechanisms behind metastasis will be obtained, leading to the future development of new therapeutic strategies.

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Acknowledgments

The authors wish to thank Ingvild Wendelbo, Tove Johansen and Bodil Hansen for technical assistance, and Ian Pryme for a critical review of the manuscript. This work was supported by The Norwegian Cancer Society; the Norwegian Research Council; Innovest AS; Strategic Research Programme; Helse-Vest; Haukeland University Hospital; the Bergen Translational Research Program; and Centre de Recherche Public de la Santé, Luxembourg.

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  1. NorLux Neuro-Oncology Laboratory, Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5019, Bergen, Norway

    Inderjit Daphu, Terje Sundstrøm, Sindre Horn, Peter C. Huszthy, Per Ø. Sakariassen, Hrvoje Miletic, Rolf Bjerkvig & Frits Thorsen

  2. NorLux Neuro-Oncology Laboratory, Centre de Recherche Public de la Santé, Luxembourg, Luxembourg

    Simone P. Niclou & Rolf Bjerkvig

  3. Department of Pathology, Haukeland University Hospital, Bergen, Norway

    Heike Immervoll & Hrvoje Miletic

  4. Department of Surgical Sciences, University of Bergen, Bergen, Norway

    Terje Sundstrøm

  5. Department of Neurosurgery, Haukeland University Hospital, Bergen, Norway

    Terje Sundstrøm

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  1. Inderjit Daphu
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Daphu, I., Sundstrøm, T., Horn, S. et al. In vivo animal models for studying brain metastasis: value and limitations. Clin Exp Metastasis 30, 695–710 (2013). https://doi.org/10.1007/s10585-013-9566-9

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