The diet-derived sulforaphane inhibits matrix metalloproteinase-9-activated human brain microvascular endothelial cell migration and tubulogenesis

被引:36
作者
Annabi, Borhane [2 ]
Rojas-Sutterlin, Shanti [1 ]
Laroche, Mathieu [1 ,3 ]
Lacharnbre, Marie-Paule [1 ]
Moumdjian, Robert [3 ]
Beliveau, Richard [1 ]
机构
[1] UQAM, Hop St Justine, Ctr Cancerol Charles Bruneau, Quebec City, PQ, Canada
[2] Univ Quebec, Dept Chim, Ctr Biomed, Oncol Mol Lab, Montreal, PQ H3C 3P8, Canada
[3] Univ Montreal, Ctr Hosp, Dept Surg, Neurosurg Serv, Quebec City, PQ, Canada
关键词
brain endothelial cells; cooption; MMP-9; sulforaphane;
D O I
10.1002/mnfr.200700434
中图分类号
TS2 [食品工业];
学科分类号
0832 ;
摘要
Human brain microvascular endothelial cells (HBMECs) play an essential role as structural and functional components of the blood-brain barrier (BBB). While disruption of the BBB by the brain tumor-secreted matrix metalloproteinase-9 (MMP-9) favors tumor invasion, the role and regulation of MMP-9 secretion by HBMEC themselves in response to carcinogens or brain tumor-derived growth factors has received little attention. Our study delineates a unique brain endothelial phenotype in that MMP-9 secretion is increased upon phorbol 12-myristate 13-acetate (PMA) treatment of HBMEC. Sulforaphane (SFN), an isothiocyanate present in broccoli which exhibits chemopreventive properties, selectively inhibited the secretion of MMP-9 but not that of MMP-2. The decrease in MMP-9 gene expression correlated with a decrease in the expression of the mRNA stabilizing factor HuR protein triggered by SFN. PMA-induced HBMEC migration was also antagonized by SFN. Silencing of the MMP-9 gene inhibited PMA-induced MMP-9 secretion, cell migration, and in vitro tubulogenesis on Matrigel. While SFN inhibited the chemoattractive abilities of brain tumor-derived growth factors, it failed to inhibit PMA-induced tubulogenesis. Our data are indicative of a selective role for SFN to inhibit MMP-9-activated, but not basal, HBMEC migration, and tubulogenesis whose actions could add to SFN's antitumor properties.
引用
收藏
页码:692 / 700
页数:9
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