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An in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia

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Abstract

The spine is the commonest site of skeletal metastatic disease and uncontrolled growth of cancer in the spine will inevitably cause pain and neurologic compromise. Improved understanding of the pathobiology behind this devastating condition is urgently needed. For this reason, the aim of this study was to establish a clinically relevant, animal model of spinal cancer. A percutaneous orthotopic injection of human breast (MDA-MB-231) or human prostate (PC-3) cancer cells was administered into the upper lumbar spine of nude mice (n = 6). Animals were monitored twice daily for general welfare, gait asymmetry or disturbance, and hindlimb weakness. After sacrifice, plain radiographs, micro-CT imaging and histological analysis of the spines were performed on each mouse. All mice recovered fully from the inoculation procedure and displayed normal gait and behaviour patterns for at least 3 weeks post-inoculation. Subsequently, between 3 and 5 weeks post-inoculation, each mouse developed evolving paralysis in their hindlimbs over 48–72 h. All followed the same pattern of decline following onset of neurological dysfunction; from gait asymmetry and unilateral hindlimb weakness, to complete unilateral hindlimb paralysis and finally to complete bilateral hindlimb paralysis. Plain radiographs, micro-CT scanning and histological analysis confirmed local tumour growth and destruction of the spine in all six mice. An in vivo mouse model of human intraosseous spinal cancer has been established forming cancers that grow within the spine and cause epidural spinal cord compression, resulting in a reproducible, evolving neurological deficit and paralysis that closely resembles the human condition.

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Acknowledgments

This work was supported by the National Health and Medical Research Council of Australia (Fellowship No. 558418), the Victorian Orthopaedic Research Trust and the Austin Health Medical Research Foundation. We thank Dr. Ali Ghasem Zadeh, Department of Medicine, University of Melbourne, Austin Health for the reconstruction of the micro-CT images.

Conflict of interest

The authors declare no conflict of interest and all procedures were approved by the Austin Health Ethics Committee (A2012-04395) and in accordance with University of Melbourne, Australia, guidelines.

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Authors and Affiliations

  1. Spinal Biology Research Laboratory, Department of Spinal Surgery, University of Melbourne Department of Surgery, Austin Health, 145 Studley Road, PO Box 5555, Heidelberg, VIC, 3084, Australia

    Davina A. F. Cossigny, Effie Mouhtouris, Sathana Dushyanthen, Augusto Gonzalvo & Gerald M. Y. Quan

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  1. Davina A. F. Cossigny
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  2. Effie Mouhtouris
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  3. Sathana Dushyanthen
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  4. Augusto Gonzalvo
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  5. Gerald M. Y. Quan
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Correspondence to Gerald M. Y. Quan.

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Cossigny, D.A.F., Mouhtouris, E., Dushyanthen, S. et al. An in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia. J Neurooncol 115, 189–196 (2013). https://doi.org/10.1007/s11060-013-1226-z

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  • DOI: https://doi.org/10.1007/s11060-013-1226-z

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