Department of Anatomy, Faculty of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Placenta. 2012 Dec;33(12):1005-11. doi: 10.1016/j.placenta.2012.08.007. Epub 2012 Oct 30.
Extravillus trophoblast (EVT) invasion plays a critical role in placental development. Integrins bind to extracellular matrix (ECM) proteins to mediate EVT cell adhesion, migration, and invasion. Changes in O-glycans on β1-integrin have been found to regulate cancer cell behavior. We hypothesize that O-glycosyltransferases can regulate EVT invasion through modulating the glycosylation and function of β1-integrin. Here, we found that the GALNT1 and GALNT2 mRNA were highly expressed in HTR8/SVneo and first trimester EVT cells. Immunohistochemstry and immunofluorescence staining showed that GALNT2 was expressed in subpopulations of EVT cells in deciduas, but not in syncytiotrophoblasts and cytotrophoblasts of placental villi. The percentage of GALNT2-positive EVT cells increased with gestational ages. Overexpression of GALNT2 in HTR8/SVneo cells significantly enhanced cell-collagen IV adhesion, but suppressed cell migration and invasion. Notably, we found that GALNT2 increased the expression of Tn antigen (GalNAc-Ser/Thr) on β1-integrin as revealed by Vicia Villosa agglutinin (VVA) binding. Furthermore, GALNT2 suppressed the phosphorylation of focal adhesion kinase (FAK), a crucial downstream signaling molecule of β1-integrin. Our findings suggest that GALNT2 is a critical initiating enzyme of O-glycosylation for regulating EVT invasion.
绒毛外滋养细胞（EVT）浸润在胎盘发育中起着关键作用。整合素与细胞外基质（ECM）蛋白结合，介导 EVT 细胞黏附、迁移和浸润。已经发现 β1-整合素上 O-聚糖的变化可以调节癌细胞的行为。我们假设 O-糖基转移酶可以通过调节 β1-整合素的糖基化和功能来调节 EVT 的浸润。在这里，我们发现 GALNT1 和 GALNT2 mRNA 在 HTR8/SVneo 和早孕 EVT 细胞中高度表达。免疫组化和免疫荧光染色显示，GALNT2 在蜕膜中的 EVT 细胞亚群中表达，但不在胎盘绒毛的合体滋养层细胞和细胞滋养层细胞中表达。GALNT2 阳性 EVT 细胞的百分比随着孕龄的增加而增加。GALNT2 在 HTR8/SVneo 细胞中的过表达显著增强了细胞与胶原蛋白 IV 的黏附，但抑制了细胞迁移和浸润。值得注意的是，我们发现 GALNT2 增加了 Vicia Villosa agglutinin（VVA）结合所揭示的 β1-整合素上 Tn 抗原（GalNAc-Ser/Thr）的表达。此外，GALNT2 抑制了 β1-整合素下游信号分子焦点黏附激酶（FAK）的磷酸化。我们的研究结果表明，GALNT2 是调节 EVT 浸润的 O-糖基化的关键起始酶。
