By downregulating MMP-9
Related researchs have showed that EBP50 could inhibit the migration and
invasion of breast cancer cells by down-regulating MMPs and interacting
with β-catenin(30,33). Since FLS migration and invasion are essential
steps leading to joint destruction of RA, we evaluated the effect of
EBP50 on these aggressive phenotypes of FLS in vitro. The primary FLS
were left untreated (CON) or transfected with LV-EBP50 or LV-Plvx for 72
h, then the migration and invasion of FLS were evaluated using the
transwell assay. FLS overexpressing EBP50 displayed dramatic reduction
in the number of migrating and invading cells across transwell assay
(Fig. 3A-3B). As we known, the FLS could express MMPs and a variety of
surface adhesion molecules to influence the migration and invasion. To
study the potential mechanisms underlying the biological effect of EBP50
in FLS, the expression of β-catenin , E-cadherin , MMP2 and MMP9 were
analyzed in LV-EBP50 and LV-Plvx transfected cells and untreated cells.
The results have showed that protein levels of β-catenin were unchanged
and E-cadherin were not expressed (Fig. 3C-3D), and the expression of
MMP-9 in the EBP50-overexpressing cells were significantly decreased,
whereas MMP-2 remained the same (Fig. 3E-3F-3G).These results have
indicated that overexpression of EBP50 impaired both the migratory and
invasive ability of FLS by downregulating MMP-9.