Eph-Ephrin A System Regulates Human Choriocarcinoma-Derived JEG-3 Cell Invasion
Eph-Ephrin A System Regulates Human Choriocarcinoma-Derived JEG-3 Cell Invasion
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DOI：
10.1097/igc.0b013e3182849e36
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发表时间：
2013-03-01
影响因子：
4.8
通讯作者：
Konishi, Ikuo
中科院分区：
文献类型：
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作者：
Fujiwara, Hiroshi;Nishioka, Yoshihiro;Konishi, Ikuo
目的：肾上腺素系统是一种独特的系统，可以诱导多种细胞反应，如细胞迁移、血管生成调节、轴突引导等。此前，Eph-EPhin系统被报道调节人类绒毛外滋养层细胞的侵袭。本研究以人绒毛膜癌细胞系JEG-3为研究对象，研究了EphEphin系统在恶性妊娠滋养细胞疾病侵袭中的作用。方法：采用逆转录-聚合酶链式反应检测JEG-3细胞A类Ephs和Ephin的表达。通过细胞增殖和Matrigel侵袭实验观察重组人Eph A1(r-Eph A1)和r-Ephin A4对JEG-3细胞增殖和侵袭能力的影响。用流式细胞仪检测r-Eph A1和r-ephin A4对JEG-3细胞整合素表达的影响。结果：逆转录-聚合酶链式反应检测到JEG-3细胞表达EphA1、A2、A4和ePhin A1、A4、A5的mRNAs。在Matrigel侵袭实验中，r-Eph A1和r-ephin A4均促进JEG-3细胞的侵袭，但不影响细胞的增殖。流式细胞仪检测显示，在r-Eph A1和r-ephin A4作用24小时后，JEG-3细胞整合素α5的表达增加。Western blotting分析显示，r-ewitin A4可诱导JEG-3细胞粘着斑激酶的去磷酸化。结论：Eph-ewitin相互作用与整合素共同参与了绒毛膜癌侵袭的调控。
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 alpha 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.