67‐kDa Laminin receptor contributes to hypoxia‐induced migration and invasion of trophoblast‐like cells by mediating matrix metalloproteinase‐9

Summary Insufficient trophoblast invasion often occurs in patients experiencing preeclampsia. The 67‐kDa laminin receptor ( LR 1) is a multifunctional protein that binds to laminin and interacts with the extracellular matrix. We recently demonstrated that LR 1 is implicated in trophoblast migration and invasion. However, whether LR 1 is involved in hypoxia‐mediated trophoblastic invasion remains unclear and requires further investigation. This study demonstrates that two trophoblast‐like cell lines ( JEG 3 and BeWo cells) cultured at 3% oxygen exerted enhanced migratory and invasive capabilities as compared with their counterparts exposed to 20% oxygen. LR 1 expression was increased in hypoxic JEG 3 cells but decreased after transfection with hypoxia‐inducible factor 1 alpha ( HIF ‐1 α ) specific si RNA . Moreover, sh RNA targeting LR 1 m RNA significantly inhibited hypoxia‐induced increase in matrix metalloproteinase ( MMP )‐9 activity in JEG 3 cells. Forced overexpression of LR 1 augmented JEG 3 cell migration and invasion, and enhanced MMP ‐9 expression and activity. Additionally, the blockade of the MMP ‐9 effect with its neutralizing antibody reduced LR 1 elevation‐promoted trophoblastic invasion. In summary, this study demonstrates that LR 1 contributes to hypoxia‐induced migration and invasion of trophoblast cells at least partly by mediating MMP ‐9 in vitro .