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The diet‐derived sulforaphane inhibits matrix metalloproteinase‐9‐activated human brain microvascular endothelial cell migration and tubulogenesis
Author(s) -
Annabi Borhane,
RojasSutterlin Shanti,
Laroche Mathieu,
Lachambre MariePaule,
Moumdjian Robert,
Béliveau Richard
Publication year - 2008
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.200700434
Subject(s) - sulforaphane , matrix metalloproteinase , matrigel , gene silencing , microbiology and biotechnology , cell migration , secretion , chemistry , endothelial stem cell , biology , cancer research , in vitro , biochemistry , gene
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.