Macrophage migration inhibitory factor up-regulates alpha(v)beta(3) integrin and vascular endothelial growth factor expression in endometrial adenocarcinoma cell line Ishikawa

详细信息    查看全文

• 作者：Patrick Kibangou Bondza ; Christine N. Metz ; Ali Akoum
• 关键词：Alpha(v)beta(3) integrin ; Endometrial cancer cells ; Macrophage migration inhibitory factor
• 刊名：Journal of Reproductive Immunology
• 出版年：2008
• 出版时间：April 2008
• 年：2008
• 卷：77
• 期：2
• 页码：142-151
• 全文大小：804 K

文摘

Human endometrium undergoes a series of dynamic physiological changes during the menstrual cycle of reproductive age women. Many factors, including hormones, cytokines, growth factors, matrix metalloproteinases and integrins, are essential for the success of embryonic implantation into endometrial tissue. Herein, we used a well-differentiated endometrial adenocarcinoma cell line, Ishikawa, to investigate in vitro the role played by macrophage migration inhibitory factor (MIF) in the regulation of endometrial receptivity markers. Quantitative real-time polymerase chain reaction (qRT-PCR) showed that MIF induced a slight increase in alpha(v) (v) mRNA integrin subunit expression during the first 12 h, but reached a significant difference after 24 h MIF treatment compared to control, whereas beta(3) (β3) integrin subunit displayed significant increase in mRNA 2 h following treatment. Immunocytofluorescence showed strong v and β3 immunostaining at 25 ng/ml MIF, and Western blotting clearly indicated increased v and β3 protein expression. MIF treatment significantly stimulated vascular endothelial growth factor (VEGF) mRNA expression in a dose- and time-dependent manner after 24 h treatment. Moreover, immunocytofluorescence revealed positive VEGF immunostaining compared to control, and analysis by ELISA of VEGF release in culture supernatants demonstrated that MIF (25 ng/ml) significantly induced VEGF secretion at 12 and 24 h. In conclusion, this study provides evidence that MIF directly up-regulates vβ3 integrin and VEGF expression in human endometrial Ishikawa cells and may advance our understanding of factors involved in the establishment of endometrial receptivity and successful implantation.