Department of Neurosurgery, Duke University Medical Center, Durham, North Carolina, USA.
Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
World Neurosurg. 2021 Nov;155:122-134. doi: 10.1016/j.wneu.2021.07.121. Epub 2021 Jul 31.
Epidural spinal cord compression (ESCC) secondary to spine metastases is one of the most devastating sequelae of primary cancer as it may lead to muscle weakness, paresthesia, pain, and paralysis. Spine metastases occur through a multistep process that can result in eventual ESCC; however, the lack of a preclinical model to effectively recapitulate each step of this metastatic cascade and the symptom burden of ESCC has limited our understanding of this disease process. In this review, we discuss animal models that best recapitulate ESCC. We start with a broad discussion of commonly used models of bone metastasis and end with a focused discussion of models used to specifically study ESCC. Orthotopic models offer the most authentic recapitulation of metastasis development; however, they rarely result in symptomatic ESCC and are challenging to replicate. Conversely, models that involve injection of tumor cells directly into the bloodstream or bone better mimic the symptoms of ESCC; however, they provide limited insight into the epithelial to mesenchymal transition and natural hematogenous spread of tumor cells. Therefore, until an ideal model is created, it is critical to select an animal model that is specifically designed to answer the scientific question of interest.
硬膜外脊髓压迫症(ESCC)继发于脊柱转移是原发性癌症最具破坏性的后遗症之一,因为它可能导致肌肉无力、感觉异常、疼痛和瘫痪。脊柱转移是通过多步过程发生的,最终可能导致 ESCC;然而,由于缺乏有效的临床前模型来有效重现这种转移级联的每个步骤,以及 ESCC 的症状负担,限制了我们对这种疾病过程的理解。在这篇综述中,我们讨论了最能重现 ESCC 的动物模型。我们首先广泛讨论了常用的骨转移模型,最后重点讨论了专门用于研究 ESCC 的模型。原位模型提供了对转移发展最真实的重现;然而,它们很少导致有症状的 ESCC,并且难以复制。相反,涉及将肿瘤细胞直接注射到血液或骨骼中的模型更好地模拟 ESCC 的症状;然而,它们对上皮到间充质转化和肿瘤细胞的自然血源性扩散提供的见解有限。因此,在创建理想模型之前,选择专门设计用于回答感兴趣的科学问题的动物模型至关重要。