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[不同多发性骨髓瘤细胞系移植小鼠的肿瘤发生分析]

[Analysis of Tumorigenesis in Mice Transplanted with Different Multiple Myeloma Cell Lines].

作者信息

An Na, Liu Jia-Jun

机构信息

Department of Hematology, The Third Affiliated Hospital of Zhongshan University, Guangzhou 510630, Guangdong Province, China,Department of Hematology, Shenzhen Second People's Hospital, Shenzhen 518035, Guangdong Province, China.

Department of Hematology, The Third Affiliated Hospital of Zhongshan University, Guangzhou 510630, Guangdong Province, China,E-mail:

出版信息

Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2019 Oct;27(5):1522-1529. doi: 10.19746/j.cnki.issn.1009-2137.2019.05.025.

Abstract

OBJECTIVE

To investigate the tumorigenicity of several multiple myeloma (MM) cell lines transplanted in mice without γ-ray irradiation and to construct the MM disease model to facilitate in vivo experiments.

METHODS

NOD/SCID or NSG mice were subcutaneously or caudally transplanted with MM cell lines (LP-1, OPM2, RPMI 8226 and MOLP8), or cell lines with luciferase (RPMI-Luc-Puro, RPMI-Luc-mCherry and MOLP8-Luc-Puro). Tumor growth was observed by measuring the tumor size with a caliper. CD138 tumor cells in peripheral blood were detected by flow cytometry. The free light chain in mouse serum was detected by immunofixation electrophoresis. Tumor type was identified by immunohistochemistry.

RESULTS

Twenty one NOD/SCID mice were subcutaneously transplanted with LP-1 cells or OPM2 cells respectively, and no tumors formed till 7 weeks after transplantation. Fifteen NOD/SCID mice subcutaneously transplanted with RPMI 8226 cells showed tumor formation one week later. As of 7 weeks, the rate of tumorigenesis was 80% (12/15). Serum λ light chain was detected and no CD138 tumor cells were detected in peripheral blood. Two NOD/SCID mice each were subcutaneously transplanted with RPMI-Luc-Puro, RPMI-Luc-mcherry and MOLP8-Luc-Puro cells respectively. No tumor signal was detected through IVIS in RPMI-Luc-mcherry cells-transplanted mice. There was tumor signal at 1 week in RPMI-Luc-Puro and MOLP8-Luc-Puro cells-transplanted mice, the former disappeared at 2 weeks and the latter persisted more than 3 weeks. NSG mice subcutaneously transplanted with both cells persistently displayed the tumor signal. Neither NOD/SCID nor NSG mice transplanted with RPMI 8226, RPMI-Luc-Puro, RPMI-Luc-mcherry or MOLP8-Luc-Puro cells through tail vein developed the tumor signal. Only one NSG mice transplanted with MOLP8-Luc-Puro cells appeared transient tumor signal.

CONCLUSION

Unirradiated mice transplanted with MM cell lines tended to develop local tumor, and failed to develop disseminated tumor. The tumorigenicity of different cell lines is quite different and the vector transfection can reduce the tumorigenic ability. NSG mice with more severe immunodeficiency are more suitable for tumor growth.

摘要

目的

研究几种多发性骨髓瘤(MM)细胞系在未进行γ射线照射的情况下移植到小鼠体内的致瘤性,并构建MM疾病模型以促进体内实验。

方法

将NOD/SCID或NSG小鼠皮下或尾静脉移植MM细胞系(LP-1、OPM2、RPMI 8226和MOLP8),或带有荧光素酶的细胞系(RPMI-Luc-Puro、RPMI-Luc-mCherry和MOLP8-Luc-Puro)。用卡尺测量肿瘤大小以观察肿瘤生长。通过流式细胞术检测外周血中的CD138肿瘤细胞。用免疫固定电泳检测小鼠血清中的游离轻链。通过免疫组织化学鉴定肿瘤类型。

结果

分别将21只NOD/SCID小鼠皮下移植LP-1细胞或OPM2细胞,移植后7周内均未形成肿瘤。15只皮下移植RPMI 8226细胞的NOD/SCID小鼠1周后出现肿瘤形成。截至7周,致瘤率为80%(12/15)。检测到血清λ轻链,外周血中未检测到CD138肿瘤细胞。分别将2只NOD/SCID小鼠皮下移植RPMI-Luc-Puro、RPMI-Luc-mcherry和MOLP8-Luc-Puro细胞。在移植RPMI-Luc-mcherry细胞的小鼠中,通过IVIS未检测到肿瘤信号。在移植RPMI-Luc-Puro和MOLP8-Luc-Puro细胞的小鼠中,1周时出现肿瘤信号,前者在2周时消失,后者持续超过3周。皮下移植这两种细胞的NSG小鼠持续显示肿瘤信号。通过尾静脉移植RPMI 8226、RPMI-Luc-Puro、RPMI-Luc-mcherry或MOLP8-Luc-Puro细胞的NOD/SCID和NSG小鼠均未出现肿瘤信号。仅1只移植MOLP8-Luc-Puro细胞的NSG小鼠出现短暂肿瘤信号。

结论

移植MM细胞系的未照射小鼠倾向于形成局部肿瘤,未能形成播散性肿瘤。不同细胞系的致瘤性差异很大,载体转染可降低致瘤能力。免疫缺陷更严重的NSG小鼠更适合肿瘤生长。

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