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 investig...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.展开更多
基金This work was supported by the Grant from National Natural Science Foundation of China (No. 30670905).
文摘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.