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.
J Neurooncol. 2013 Nov;115(2):189-96. doi: 10.1007/s11060-013-1226-z. Epub 2013 Aug 18.
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.
脊柱是骨骼转移疾病最常见的部位，癌症在脊柱的不受控制的生长将不可避免地导致疼痛和神经功能损害。迫切需要深入了解这种破坏性疾病的病理生物学。出于这个原因，本研究的目的是建立一种临床相关的脊柱癌症动物模型。通过皮内原位注射将人乳腺癌（MDA-MB-231）或人前列腺癌（PC-3）细胞注入裸鼠的上腰椎（n = 6）。每天两次监测动物的一般福利、步态不对称或紊乱以及后肢无力。处死动物后，对每只小鼠的脊柱进行普通 X 线、微 CT 成像和组织学分析。所有接种后的小鼠均从接种过程中完全恢复，并且在接种后至少 3 周内表现出正常的步态和行为模式。随后，在接种后 3 至 5 周，每只小鼠在 48-72 小时内逐渐出现后肢瘫痪。所有小鼠在出现神经功能障碍后都遵循相同的下降模式；从步态不对称和单侧后肢无力，到单侧后肢完全瘫痪，最后到双侧后肢完全瘫痪。普通 X 线、微 CT 扫描和组织学分析证实了所有 6 只小鼠的脊柱局部肿瘤生长和破坏。建立了一种人脊柱内骨内癌症的活体小鼠模型，形成了在脊柱内生长并导致硬膜外脊髓压迫的癌症，导致可重现的、进行性的神经功能缺损和瘫痪，非常类似于人类的情况。
