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A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion

  • Laboratory Investigation - Human/Animal Tissue
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Abstract

Glioblastoma multiforme (GBM) is a rapidly progressive disease of morbidity and mortality and is the most common form of primary brain cancer in adults. Lack of appropriate in vivo models has been a major roadblock to developing effective therapies for GBM. A new highly invasive in vivo GBM model is described that was derived from a spontaneous brain tumor (VM-M3) in the VM mouse strain. Highly invasive tumor cells could be identified histologically on the hemisphere contralateral to the hemisphere implanted with tumor cells or tissue. Tumor cells were highly expressive for the chemokine receptor CXCR4 and the proliferation marker Ki-67 and could be identified invading through the pia mater, the vascular system, the ventricular system, around neurons, and over white matter tracts including the corpus callosum. In addition, the brain tumor cells were labeled with the firefly luciferase gene, allowing for non-invasive detection and quantitation through bioluminescent imaging. The VM-M3 tumor has a short incubation time with mortality occurring in 100% of the animals within approximately 15 days. The VM-M3 brain tumor model therefore can be used in a pre-clinical setting for the rapid evaluation of novel anti-invasive therapies.

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Abbreviations

CT-2A:

Mouse astrocytoma

CXCR4:

Chemokine receptor

GBM:

Glioblastoma multiforme

IGFBP-2:

Insulin-like growth factor binding protein 2

Ki-67:

Proliferation marker

VM-M3:

Invasive mouse malignant glioma

VM-M3/Fluc:

VM-M3 tumor cells labeled with firefly luciferase

VM-NM1:

Mouse malignant glioma

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Acknowledgements

This work was supported from NIH Grants [NS-055195; CA-102135] and from the Boston College Research expense fund. The authors would like to thank Roderick Bronson for technical advice and evaluation of tumor histology.

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Authors and Affiliations

  1. Boston College, Higgins Hall 140 Commonwealth Ave., Chestnut Hill, MA, 02467, USA

    Laura M. Shelton, Purna Mukherjee, Leanne C. Huysentruyt, Ivan Urits, Joshua A. Rosenberg & Thomas N. Seyfried

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  1. Laura M. Shelton
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  2. Purna Mukherjee
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  3. Leanne C. Huysentruyt
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Correspondence to Thomas N. Seyfried.

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Shelton, L.M., Mukherjee, P., Huysentruyt, L.C. et al. A novel pre-clinical in vivo mouse model for malignant brain tumor growth and invasion. J Neurooncol 99, 165–176 (2010). https://doi.org/10.1007/s11060-010-0115-y

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