Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines

Fertil Steril. 2014 Mar;101(3):874-82. doi: 10.1016/j.fertnstert.2013.12.015. Epub 2014 Jan 11.


Objective: To investigate the role of MFG-E8 and its receptor integrin αvβ3 in the attachment of trophoblast cells to the endometrial epithelium.

Design: Experimental in vitro study.

Setting: Academic center.

Patient(s): None.

Intervention(s): By using a well-differentiated endometrial adenocarcinoma cell line (Ishikawa cells) and choriocarcinoma human trophoblast cells (Jar cells), an in vitro assay mimicking human implantation was established. To investigate the impact of blocking MFG-E8 and integrin αvβ3, we pretreated the cell lines with antibodies against those proteins at different concentrations before the attachment assay.

Main outcome measure(s): Attachment rate of Jar spheroids to the epithelial cell monolayer.

Result(s): Pretreatment of Ishikawa cells with anti-MFG-E8 antibody caused a dose-dependent and significant inhibition of attachment. On the other hand, pretreatment of Jar spheroids did not result in a significant effect on the attachment rate. Pretreatment of Ishikawa cells as well as Jar spheroids with anti-integrin αvβ3 antibodies resulted in a dose-dependent, significant inhibition of attachment.

Conclusion(s): This study showed that blocking MFG-E8 and its receptor integrin αvβ3 in Ishikawa cells diminishes Jar spheroid attachment. Moreover, blocking integrin αvβ3 in the trophoblastic cells also diminished their attachment to the Ishikawa monolayer.

Keywords: Attachment; Jar spheroids; MFG-E8; human endometrium; implantation; integrin αvβ3.

MeSH terms

  • Antibodies, Neoplasm
  • Antigens, Surface / immunology
  • Antigens, Surface / physiology*
  • Cell Line, Tumor
  • Coculture Techniques
  • Embryo Implantation / immunology*
  • Endometrium / metabolism*
  • Epithelial Cells / metabolism
  • Female
  • Humans
  • Integrin alphaVbeta3 / antagonists & inhibitors
  • Integrin alphaVbeta3 / immunology
  • Integrin alphaVbeta3 / physiology*
  • Milk Proteins / antagonists & inhibitors
  • Milk Proteins / immunology
  • Pregnancy
  • Trophoblasts / metabolism*


  • Antibodies, Neoplasm
  • Antigens, Surface
  • Integrin alphaVbeta3
  • MFGE8 protein, human
  • Milk Proteins