Interaction of Pregnancy-Specific Glycoprotein 1 With Integrin α5β1 Is a Modulator of Extravillous Trophoblast Functions

Abstract

Human pregnancy-specific glycoproteins (PSGs) serve immunomodulatory and pro-angiogenic functions during pregnancy and are mainly expressed by syncytiotrophoblast cells. While PSG mRNA expression in extravillous trophoblasts (EVTs) was reported, the proteins were not previously detected. By immunohistochemistry and immunoblotting, we show that PSGs are expressed by invasive EVTs and co-localize with integrin α5. In addition, we determined that native and recombinant PSG1, the most highly expressed member of the family, binds to α5β1 and induces the formation of focal adhesion structures resulting in adhesion of primary EVTs and EVT-like cell lines under 21% oxygen and 1% oxygen conditions. Furthermore, we found that PSG1 can simultaneously bind to heparan sulfate in the extracellular matrix and to α5β1 on the cell membrane. Wound healing assays and single-cell movement tracking showed that immobilized PSG1 enhances EVT migration. Although PSG1 did not affect EVT invasion in the in vitro assays employed, we found that the serum PSG1 concentration is lower in African-American women diagnosed with early-onset and late-onset preeclampsia, a pregnancy pathology characterized by shallow trophoblast invasion, than in their respective healthy controls only when the fetus was a male; therefore, the reduced expression of this molecule should be considered in the context of preeclampsia as a potential therapy.

The Involvement of Cell Adhesion Molecules, Tight Junctions, and Gap Junctions in Human Placentation

“…α5β1 promotes trophoblast adhesion and invasion by interacting with other molecules. For instance, the α5 subunit colocalizes and interacts with pregnancy-specific glycoprotein-1 to promote the adhesion of the EVTs to the decidual cells [28]. On the other hand, the β1 subunit associates with A disintegrin and metalloproteinase domain-8 (ADAM8) during the initial stages of cell-matrix attachment, suggesting that ADAM8 may enhance β1 subcellular localization to actin-rich structures or may regulate the configuration of β1 [29].…”

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

“…Second, the bound form of CEACAM enhances the KC microenvironment by activating fibroblasts, which in turn facilitate CRC growth (139,141). ECM expression of the α5β1 integrin/fibronectin interaction then leads to cell survival (142)(143)(144). Finally, CEACAM5 upregulates adhesion molecules such as E-cadherin and N-cadherin, thereby promoting aggregation (cell survival) and metastasis (139,140,(144)(145)(146).…”

Detection of mitochondrial coupling factor 6 in placental tissues from preeclamptic pregnancies and its influence on biological behavior of trophoblast cells

“…During adhesion of the late blastocyst to the endometrium, trophoblast cells begin to differentiate and invade the endometrium, the 1/3 of the uterine muscle layer and the vascular system, which ensures a sufficient blood supply to the placenta, maintaining normal embryo development ( 1 , 2 ). Previous studies have revealed that an invasive insufficiency of trophoblast cells can lead to the occurrence of preeclampsia ( 3 , 4 ). Moreover, it has been shown that hypoxia can lead to an insufficiency in invasion in the trophoblast cells ( 1 ).…”