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

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.

journal_name

Leuk Lymphoma

journal_title

Leukemia & lymphoma

authors

Wang C,Cai X,Chen B,He Z,Chen Z,Cen J,Li Z

doi

10.3109/10428194.2013.783214

subject

Has Abstract

pub_date

2013-12-01 00:00:00

pages

2707-11

issue

12

eissn

1042-8194

issn

1029-2403

journal_volume

54

pub_type

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