TY - JOUR T1 - Eph-Ephrin A System Regulates Human Choriocarcinoma–Derived JEG-3 Cell Invasion JF - International Journal of Gynecologic Cancer JO - Int J Gynecol Cancer SP - 576 LP - 582 DO - 10.1097/IGC.0b013e3182849e36 VL - 23 IS - 3 AU - Hiroshi Fujiwara AU - Yoshihiro Nishioka AU - Hisanori Matsumoto AU - Koh Suginami AU - Akihito Horie AU - Hirohiko Tani AU - Noriomi Matsumura AU - Tsukasa Baba AU - Yukiyasu Sato AU - Yoshihiko Araki AU - Ikuo Konishi Y1 - 2013/03/01 UR - http://ijgc.bmj.com/content/23/3/576.abstract N2 - Objectives The Eph-ephrin system is a unique system that can induce multiple cellular responses such as cell migration, regulation of angiogenesis, and axonal guidance. Previously, the Eph-ephrin system was reported to regulate human extravillous trophoblast invasion. In this study, we examined the possible involvement of the Eph-ephrin system in the invasion of malignant gestational trophoblastic diseases using a human choriocarcinoma–derived cell line, JEG-3.Methods The mRNA expression of class A Ephs and ephrins on JEG-3 cells was examined by reverse transcription–polymerase chain reaction. The effects of recombinant human Eph A1 (r-Eph A1) and r-ephrin A4 on the proliferation and invasion of JEG-3 cells were investigated by cell proliferation and Matrigel invasion assays. The alterations of integrin expression on JEG-3 cells in the presence of r-Eph A1 and r-ephrin A4 were investigated by flow cytometry. The induction of phosphorylation of focal adhesion kinase in JEG-3 cells by r-ephrin A4 was examined by Western blot analysis.Results By reverse transcription–polymerase chain reaction, mRNAs of Eph A1, A2, and A4 and ephrin A1, A4, and A5 were detected on JEG-3 cells. In Matrigel invasion assay, both r-Eph A1 and r-ephrin A4 promoted the invasion of JEG-3 cells without affecting cell proliferation. During 24-hour culture with r-Eph A1 and r-ephrin A4, the increase in integrin α 5 expression on JEG-3 cells was observed by flow cytometry. Western blotting analysis showed that r-ephrin A4 induced dephosphorylation of focal adhesion kinase in JEG-3 cells.Conclusions These findings suggest that Eph-ephrin interaction plays some role in the regulation of choriocarcinoma invasion in cooperation with integrins. ER -