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.

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.