The chemokine CXCL6 restricts human trophoblast cell migration and invasion by suppressing MMP-2 activity in the first trimester

Abstract

Can the chemokine CXCL6 affect trophoblast cell migration and invasion in human first-trimester placenta? Chemokine CXCL6 inhibits trophoblast cell migration and invasion by suppressing matrix metalloproteinase (MMP)-2 activity in human first-trimester placenta. Several chemokines including CXCL8, CXCL12, CXCL14, CXCL16, CX3CL1, CCL14 and CCL4 can promote or inhibit trophoblast cell migration and invasion in human first-trimester placenta. We used the trophoblast cell line HTR8/SVneo cells, primary trophoblast cells and villi explants to investigate the effect of rhCXCL6 on trophoblast cell migration and invasion. First, the CXCL6 RNA transcript level was detected in HTR8/SVneo cells derived from human first-trimester, second-trimester and third-trimester placenta by RT-PCR. Protein expression of CXCL6 and its receptors was tested in first-trimester placenta by immunohistochemistry. Secreted CXCL6 protein was detected in HTR8/SVneo cell supernatants by enzyme-linked immunosorbent assay. Secondly, the effect of rhCXCL6 on HTR8/SVneo cell proliferation was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Thirdly, the effect of rhCXCL6 on cell migration and invasion of HTR8/SVneo cells, primary trophoblast cells and villi explants was tested by transwell migration and invasion assays, respectively. Last, MMP-2 and MMP-9 activity in the supernatants of HTR8/SVneo and primary trophoblast cells treated by rhCXCL6 in the invasion assay was assessed by gelatin zymography. Abundance of the CXCL6 RNA transcript increased with pregnancy development. CXCL6 and its receptor were expressed in several cells at the human maternal-fetal interface. RhCXCL6 inhibited trophoblast cell migration and invasion by suppressing MMP-2 activity. These experiments are only in vitro. According to the literature, CXCL6 could promote tumour cell migration and invasion by accelerating MMP-9 activity. However, CXCL6 inhibited trophoblast cell migration and invasion by suppressing MMP-2 activity in human first-trimester interface. These data suggest that strict regulation of CXCL6 is required for normal migration and invasion of cells, such as those involved at the maternal-fetal interface.