CCL17 Induces Trophoblast Migration and Invasion by Regulating Matrix Metalloproteinase and Integrin Expression in...

Chemokines and chemokine receptors have been implicated a pivotal role in trophoblast differentiation and in the formation of a functionally normal placenta. In this study, we present data that highlight the involvement of chemokine ligand 17/chemokine receptor 4 (CCL17/CCR4) expression at the fetomaternal interface and expand its biological relevance of influence during trophoblast differentiation and placentation. By immunohistochemistry, we found that CCL17 was abundantly expressed in the decidua and trophoblasts, especially in cell columns. The receptor for CCL17, CCR4, was specifically expressed in invading interstitial extravillous trophoblasts. Furthermore, by transwell migration, invasion assays, and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, we found that exogenous CCL17 concentrations paralleled the invasive potential of cytotrophoblasts to some extent, with no significant effect on cell proliferation. Using Western blotting, we demonstrated that the stimulatory effect of CCL17 was related to the expression of matrix metalloproteinase 2 (MMP-2), MMP-13, integrin α5, and integrin β1, although it downregulated tissue inhibitors of MMP-1 expression. In conclusion, our findings suggest that CCL17, as a differentiation-related molecule coexpressed by decidua and trophoblast, stimulates extravillous trophoblast migration and directs invasion mainly via modulating integrins, MMPs, and its inhibitor levels.