Up-regulation of tissue inhibitor of metalloproteinase-2 promotes SHI-1 cell invasion in nude mice

• Published in: Leukemia & lymphoma 2013-12, Vol.54 (12), p.2707-2711
• Main Authors: Wang, Chunling, Cai, Xiaohui, Chen, Baoan, He, Zhengmei, Chen, Zixing, Cen, Jiannong, Li, Zhenjiang
• Format: Article
• Language: English
• Subjects: Animals; Cell Line, Tumor; Disease Models, Animal; Gene Expression Regulation, Leukemic; Humans; infiltration; invasion; Leukemia; Leukemic Infiltration; Leukocyte Common Antigens - metabolism; Mice; Mice, Nude; MMP-2; Myeloid-Lymphoid Leukemia Protein - genetics; Neoplasm Invasiveness; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - mortality; Neoplasms - pathology; Oncogene Proteins, Fusion - genetics; TIMP-2; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue Inhibitor of Metalloproteinase-2 - metabolism; Up-Regulation
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2013.783214

Abstract The role of tissue inhibitor of metalloproteinase-2 (TIMP-2) in extramedullary infiltration of acute leukemia is unclear. We demonstrated in our previous study that the up-regulation of TIMP-2 promoted SHI-1 cell invasion in vitro. We investigated in the present study whether TIMP-2 would have the same effect in vivo. A retroviral vector carrying human TIMP-2 cDNA was constructed and transfected into SHI-1 cells. Three subclone cells (S1, S2 and S3) that highly expressed TIMP-2 were selected to establish nude mouse models of acute leukemia. Times of leukemic onset in mice of S1, S2 and S3 groups were all earlier than that of the SHI-1 group, whereas the survival times of S1, S2 and S3 groups were all shorter than that of the SHI-1 group (p < 0.05). Histopathological results demonstrated severe leukemic infiltration in numerous organs in each group. Reverse transcription polymerase chain reaction (RT-PCR) assay showed that several organs expressed the MLL/F6 fusion gene. Moreover, the numbers of organs infiltrated by leukemic cells in S1, S2 and S3 groups were more than those in the SHI-1 group (p < 0.05). Up-regulating TIMP-2 expression enhanced SHI-1 cell invasion in nude mice and resulted in more severe leukemia infiltration. This phenomenon suggests that targeted therapy with TIMP-2 for acute leukemia should be performed with prudence.