Zhao Hongyu, Cai Weisong, Li Shuai, Da Zuke, Sun Hanxue, Ma Liang, Lin Yaoxin, Zhi Debao
Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, China.
Childs Nerv Syst. 2012 Dec;28(12):2047-54. doi: 10.1007/s00381-012-1909-3. Epub 2012 Sep 16.
To improve the therapy of advanced neuroblastoma (NB), it is critical to develop animal models that mimic NB bone metastases. Unlike the human disease, NB xenograft models rarely metastasize spontaneously to bone from the orthotopic site of primary tumor growth.
Single-cell suspensions of SY5Y, KCNR NB cells were injected directly into the femur of nude mice. Radiological and histological analyses and immunohistochemistry analyses were performed to characterize these osseous NB models. SY5Y and KCNR result in osteolytic responses.
We have detected osteoprotegerin, receptor activator of nuclear factor kappa B ligand, parathyroid hormone-related protein, and endothelin-1, proteins associated with bone growth and osteolysis, and C-X-C chemokine receptor type 4 (CXCR4) involved in tumor growth and tumor cell migration in the NB cells grown in the bone.
These animal models can be used to study biological interactions, pathways, and potential therapeutic targets and also to evaluate new agents for treatment and prevention of NB bone metastasis.
为改善晚期神经母细胞瘤（NB）的治疗方法，开发能够模拟NB骨转移的动物模型至关重要。与人类疾病不同，NB异种移植模型很少从原发性肿瘤生长的原位自发转移至骨骼。
将SY5Y、KCNR NB细胞的单细胞悬液直接注射到裸鼠的股骨中。进行放射学、组织学分析及免疫组化分析以表征这些骨NB模型。SY5Y和KCNR会引发溶骨性反应。
我们在骨骼中生长的NB细胞中检测到了骨保护素、核因子κB受体活化因子配体、甲状旁腺激素相关蛋白和内皮素-1，这些蛋白与骨生长和骨溶解相关，还检测到了参与肿瘤生长和肿瘤细胞迁移的C-X-C趋化因子受体4（CXCR4）。
这些动物模型可用于研究生物学相互作用、信号通路及潜在治疗靶点，还可用于评估治疗和预防NB骨转移的新药物。
