Is galectin-1 a trigger for trophoblast cell fusion?: the MAP-kinase pathway and syncytium formation in trophoblast tumour cells BeWo

• Published in: Molecular human reproduction 2011-12, Vol.17 (12), p.747-757
• Main Authors: Fischer, Isabelle, Weber, Maja, Kuhn, Christina, Fitzgerald, Justine S., Schulze, Sandra, Friese, Klaus, Walzel, Hermann, Markert, Udo R., Jeschke, Udo
• Format: Article
• Language: English
• Subjects: Butadienes - pharmacology; Cell Differentiation - drug effects; Cell Fusion; Choriocarcinoma - genetics; Choriocarcinoma - metabolism; Choriocarcinoma - pathology; Enzyme Inhibitors - pharmacology; ets-Domain Protein Elk-1 - agonists; ets-Domain Protein Elk-1 - genetics; ets-Domain Protein Elk-1 - metabolism; Female; Galectin 1 - metabolism; Galectin 1 - pharmacology; Gene Expression Regulation, Neoplastic - drug effects; Giant Cells - cytology; Giant Cells - drug effects; Giant Cells - metabolism; Glycogen Synthase Kinase 3 - antagonists & inhibitors; Glycogen Synthase Kinase 3 - genetics; Glycogen Synthase Kinase 3 - metabolism; Humans; Janus Kinase 2 - genetics; Janus Kinase 2 - metabolism; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - genetics; Mitogen-Activated Protein Kinases - metabolism; Nitriles - pharmacology; Phosphorylation - drug effects; Pregnancy; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Signal Transduction - genetics; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Tumor Cells, Cultured; Uterine Neoplasms - genetics; Uterine Neoplasms - metabolism; Uterine Neoplasms - pathology
• ISSN: 1360-9947; 1460-2407
• DOI: 10.1093/molehr/gar053

Galectin-1 (gal-1), a member of the mammalian β-galactoside-binding proteins, exerts biological effects by recognition of glycan ligands, including those involved in cell adhesion and growth regulation. In a previous study, we demonstrated that gal-1 induces cell differentiation processes on the membrane of choriocarcinoma cells BeWo, including the receptor tyrosine kinases, REarranged during transfection, janus kinase 2 and vascular endothelial growth factor receptor 3. Within this study, we examined which mitogen-activated protein kinases (MAPK) and serine/threonine kinases were phoshorylated by gal-1. Out of a number of 21 different MAPKs and other serine/threonine kinases, the stimulation of BeWo cells with gal-1 showed a significant alteration of signal intensity in extracellular-regulated kinases 1/2 (ERK1/2), Akt-3, Akt-pan and glycogen synthase kinase-α/β (GSK-3α/β). We demonstrated that gal-1 significantly inhibited ERK1/2, Akt-3/pan and GSK-3α/β phosphorylation in BeWo cells and in addition induced Elk1 transcription factor activation. In contrast to gal-1 effects, MAPK inhibitor U0126 reduced syncytium formation of BeWo cells. The results of our data showed that phosphorylation of MAP kinases are involved in gal-1-induced signal transduction processes in BeWo cells. Additional results obtained with MAPK inhibitor U0126 close the gap between syncytium formation induced by gal-1 and MAPK activation in trophoblast cells. Furthermore, we demonstrated that gal-1 induces the activation of Elk1, a transcription factor that is activated by MAPK pathways.