title: An in vivo mouse model of intraosseous spinal cancer causing evolving paraplegia.
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.
authors: 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.
authors: Davina A F
authors: DA
authors: Cossigny
authors: Effie
authors: E
authors: Mouhtouris
authors: Sathana
authors: S
authors: Dushyanthen
authors: Augusto
authors: A
authors: Gonzalvo
authors: Gerald M Y
authors: GM
authors: Quan
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010264:Paraplegia / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology; D011859:Radiography; D013125:Spinal Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology*; D014407:Tumor Cells, Cultured
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