Up-regulation of TIMP-2 expression promotes SHI-1 leukemic cells proliferation and infiltration in immunodeficiency mice  

作　　者：Li Zhenjiang Chen Zixing Cen Jiannong He Jun Qiu Qiaocheng Xue Yongquan 

机构地区：[1]Department of Hematology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China [2]Leukemia Researcta Unit. Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215600, China

出　　处：《Chinese Medical Journal》2014年第24期4243-4249,共7页中华医学杂志（英文版）

基　　金：This work was supported by the Grant from National Natural Science Foundation of China （No. 30670905）.

摘　　要：Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.Background MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP- 2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro. Methods A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-I. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-traated nu/nu mice to investigate the infiltration ability feature in vitro. Results The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over- expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice. Conclusion Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.

关 键 词：acute monocytic leukemia extramedullary infiltration TIMP-2 nude mice model 

分 类 号：R733.7[医药卫生—肿瘤]