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Eph-Ephrin A System Regulates Human Choriocarcinoma–Derived JEG-3 Cell Invasion
  1. Hiroshi Fujiwara, MD*,
  2. Yoshihiro Nishioka, MD*,,
  3. Hisanori Matsumoto, MD*,
  4. Koh Suginami, MD*,
  5. Akihito Horie, MD*,
  6. Hirohiko Tani, MD*,
  7. Noriomi Matsumura, MD*,
  8. Tsukasa Baba, MD*,
  9. Yukiyasu Sato, MD*,
  10. Yoshihiko Araki, MD and
  11. Ikuo Konishi, MD*
  1. *Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Kyoto;
  2. Nishioka Clinic, Osaka; and
  3. Institute for Environmental & Gender-Specific Medicine, Juntendo University Graduate School of Medicine, Urayasu, Japan.
  1. Address correspondence and reprint requests to Hiroshi Fujiwara, MD, Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8507, Japan. E-mail: fuji{at}


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.

  • Eph
  • Ephrin
  • Gestational trophoblastic disease
  • Invasion
  • JEG-3 cell

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  • This work was supported in part by Grants-in-Aid for Scientific Research (20390434 and 23390389).