A color-coded orthotopic nude-mouse treatment model of brain-metastatic paralyzing spinal cord cancer that induces angiogenesis and neurogenesis

Abstract

Objective: Cancer of the spinal cord is highly malignant and often leads to paralysis and death. A realistic mouse model would be an important benefit for the better understanding and treatment of spinal cord glioma. Materials and methods: To develop an imageable, patient-like model of this disease, U87 human glioma tumour fragments (expressing red fluorescent protein), were transplanted by surgical orthotopic implantation into the spinal cord of nontransgenic nude mice or transgenic nude mice expressing nestin-driven green fluorescent protein (ND-GFP). In ND-GFP mice, GFP is expressed in nascent blood vessels and neural stem cells. The animals were treated with temozolomide or vehicle control. Results: The intramedullary spinal cord tumour grew at the primary site, caused hind-limb paralysis and also metastasized to the brain. Temozolomide inhibited tumour growth (P < 0.01) and prevented metastasis, as well as prevented paralysis in four mice and delayed paralysis in two mice of the six tested (P = 0.005). In the ND-GFP-expressing host, ND-GFP cells staining positively for neuronal class III-β-tubulin or CD31, surrounded the tumour. These results suggest that the tumour stimulated both neurogenesis and angiogenesis, respectively. Conclusion: A patient-like model of spinal cord glioma was thus developed, which can be used for the discovery of new agents, including those that inhibit invasion and metastasis of the disease as well as those that prevent paralysis. © 2008 Blackwell Publishing Ltd.