TIMP-2基因对白血病细胞系SHI-1细胞在裸鼠体内生长的调节作用  

Biphasic effect of T1MP-2 on the growth of leukemic SHI-1 cells in nude mice

作　　者：李振江[1] 陈子兴[1] 岑建农[1] 何军[1] 邱桥成[1] 姚利[1] 

机构地区：[1]苏州大学附属第一医院江苏省血液研究所,江苏苏州251006

出　　处：《中华血液学杂志》2008年第6期370-374,共5页Chinese Journal of Hematology

基　　金：基金项目：国家自然科学基金（30670905）;江苏省卫生厅基金（H200327）

摘　　要：目的研究高表达组织型基质金属蛋白酶抑制剂-2（TIMP-2）基因对人急性单核细胞白血病细胞系SHI-1细胞在裸鼠体内浸润能力的影响。方法①经尾静脉将转染TIMP-2基因的SHI-1（SHI-1-TIMP-2）细胞与转染空载体MSCV的SHI-1（SHI-1-MSCV）细胞1×10^7分别接种于经切脾、环磷酰胺腹腔注射和全身亚致死量照射等预处理的6周龄裸鼠体内。接种后第30天各组处死8只裸鼠，其余8只观察生存期，通过病理学检测及CIM5抗体免疫组织化学染色检测SHI-1细胞在裸鼠体内各脏器中浸润情况，并对中枢神经系统白血病（CNSL）进行分级。②将5×10^6个SHI-1-TIMP-2和SHI-1-MSCV细胞分别接种于未经预处理的6周龄裸鼠前肢腋侧皮下，各组10只。分别于第23及30天各处死5只，测量肿瘤体积，并行TIMP-2及vWF抗体免疫组化染色，观察TIMP-2蛋白表达及微血管密度。结果经尾静脉接种SHI-1-TIMP-2细胞的裸鼠生存期较接种SHI-1-MSCV细胞者明显缩短，体内各脏器中成瘤增加，苏木精-伊红染色及CIM5抗体免疫组化染色显示脏器中白血病细胞浸润增加，CNSL发生程度更严重。接种于裸鼠皮下时，尽管SHI-1-TIMP-2细胞成瘤时间提前，其在第23及30天时所形成的瘤块体积较SHI-1-MSCV细胞组显著减少，并出现中央坏死区，免疫组化染色示瘤块TIMP-2蛋白表达增加，而微血管密度减少。结论TIMP-2基因具有多样性，在肿瘤细胞浸润及其转移中似有双相调节作用。Objective To investigate the influence of tissue inhibitor of metalloproteinase 2 （TIMP-2） on the infiltrative patterns of human monocytic leukemic cell line SHI-1 in nude mice. Methods ①1×10^7 TIMP-2 gene transduced SHI-1 （SHI-1-TIMP-2） and SHI-1 transduced MSCV gene （SHI-1-MSCV） cells were inoculated via tail vein into 6-weed nude mice, which pretreated by splenectomy, cytoxan intraperitoneal injection, and sublethal irradiation（ referred as SCI nude mice）. 30 days after inoculation, half of the mice were sacrificed, and the infiltration patterns were investigated by histological exam and human CD45 immuno- histochemistry, other mice were observed for survival time. ②Leukemic cells inoculated subcutaneously into the axillary area of mice without any pre-treatment. On day 23 and 30, mice were sacrificed to measure the volume of neoplasm. TIMP-2 protein expression and the micro vein density were detected by immunohlsto- chemistry. Results In SCI nude mice inoculated via caudal vein with SHI-1-TIMP-2 cells, the survival time was shorter and infiltration （including in central nervous system）was higher than that in those inoculated with SHI-1-MSCV cells. However, in inoculated subcutaneously group,the neoplasm though grew rapidly at first, over expression of TIMP-2 limited the tumor growth and angiogenesis. Conclusion The functions of TIMP-2 are diversity; the role of TIMP-2 in tumor infiltration and metastasis was worthy of further investigation.

关 键 词：白血病 单核细胞 急性 白血病浸润 基因 TIMP-2 模型 动物 

分 类 号：R686[医药卫生—骨科学]