人类神经母细胞瘤骨侵袭与转移模型的建立和评价

Establishment and evaluation of bone invasion/metastasis model for human neuroblastoma

目的:探讨如何建立适合长期研究与治疗的人类神经母细胞瘤(NB)骨侵袭/转移的动物模型。方法:将SMS-KCNR和SMS-SAN细胞采用骨髓腔内注射和静脉注射的方法分别种植到雌性无胸腺裸鼠及Cb-17/IcrHsd-重度联合免疫缺陷(SCID)变异小鼠体内。通过观测放射影像学表现、HE染色病理组织切片,观察肿瘤细胞对骨的侵袭情况,应用Kaplan-Meier曲线分析及Log-rank检验,对实验动物进行生存状况分析。结果:SMS-SAN和SMS-KCNR细胞系细胞在骨髓内直接种植后在全部试验动物中均可以侵袭骨质形成溶骨性病变;同样,在静脉注射后2种细胞系细胞均可以在部分实验动物体内(SMS-SAN:5只;SMS-KCNR:6只)经血行转移到骨或骨髓,并进一步侵袭骨皮质。在骨侵袭模型和骨转移模型之间,2种细胞在无进展生存时间上差异有统计学意义,P<0.000 1;总生存时间的比较上差异也有统计学意义,P<0.000 1。结论:模型的建立极好地模拟了人类NB侵袭和转移的特性,加深了NB骨转移、侵袭机制的理解。

OBJECTIVE：To establish bone invasion and metastasis animal model of neuroblastoma（NB） for long-term research and treatment.METHODS：SMS-SAN and SMS-KCNR NB cells were inoculated into bone marrow cavity and tail vein,respectively.High-resolution radiographic imaging and HE staining were utilized to observe bone invasion and metastasis features,kaplan-meier curve analysis and log-rank test were used to evaluate progression-free survival and overall survival between bone invasion and bone metastasis models.RESULTS：All of 5 animals were able to form osteolytic lesions in bone invasion models in both NB cell lines,respectively,both of NB cell lines develop metastasis in bones of part of xenograft models（SMS-SAN： 5,SMS-KCNR： 6）injected systemically,respectively.Regardless of SMS-SAN and SMS-KCNR cells lines,between two group xenograft models there was significant difference in progression-free survival analysis,and in overall survival analysis（P0.000 1）.CONCLUSION：This model mimic human NB invasive and metastatic characteristics,will increase our understanding of the biology of bone metastases mechanism.