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Up-regulation of Tissue Inhibitor of metalloproteinase-2 Promotes SHI-1 Cell Invasion in Nude Mice

Up-regulation of Tissue Inhibitor of metalloproteinase-2 Promotes SHI-1 Cell Invasion in Nude Mice

Chunling Wang, Xiaohui Cai, Baoan Chen, Zhengmei He, Zixing Chen, Jiannong Cen, Zhenjiang Li

Leuk Lymphoma. 2013 Dec;54(12):2707-11.

PMID: 23472970

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4241311	Tissue Inhibitor of Metalloproteinase-2 human			Price

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