ADATMS-7 regulates the focal adhesion kinase signaling and promotes invasiveness of trophoblasts in early pregnancy

Introduction: ADAMTS-7, a member of the disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family, was recently identified to be associated with cell migration and invasion. However, its function on trophoblasts remains unknown. In this study, we are aimed to investigate the role of ADAMTS-7 on trophoblasts in human first trimester gestation. Methods: The expression of ADAMTS-7 in trophoblasts and HTR8/SVneo cells is examined by immunohistochemistry and quantitative real-time PCR. BrdU incorporation and Annexin V/PI staining are utilized to measure the effect of ADAMTS-7 on the proliferation and apoptosis of HTR8/SVneo cells, respectively. In addition, we detect the role of ADAMTS-7 on the invasion ability of HTR8/SVneo cells using matrigel invasion assays. The activation of focal adhesion kinase (FAK) and integrin beta 1 induced by ADAMTS-7 were determined by Western blot. Results: ADAMTS-7 and its substrate cartilage oligomeric matrix protein (COMP) were expressed in both primary human trophoblasts and human trophoblast cell lines. TGF-beta 1 induced a continuous and significant decrease of ADAMTS-7. Inversely, IL-1 beta up-regulated the ADAMTS-7 level in a dosage dependent manner. In addition, knockdown of ADAMTS-7 inhibited the growth and invasion of HTR8/SVneo cells. To the contrary, ADAMTS-7 overexpression promoted the growth and invasion of HTR8/SVneo cells. ADAMTS-7 knockdown led to a decreased level of FAK Tyr-397 phosphorylation. Discussion: Our results suggest that ADAMTS-7 may regulate trophoblasts invasion through focal adhesion kinase (FAK) signaling.