| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
From the Departments of Obstetrics and Gynecology,* Medical and Chemical Laboratory Diagnostics, and Clinical Pathology, Medical University of Vienna, Vienna, Austria
The molecular mechanisms governing invasive differentiation of human trophoblasts remain largely elusive. Here, we investigated the role of Wnt-ß-catenin-T-cell factor (TCF) signaling in this process. Reverse transcriptase-polymerase chain reaction and Western blot analyses demonstrated expression of Wnt ligands, frizzled receptors, LRP-6, and TCF-3/4 transcription factors in total placenta and different trophoblast cell models. Immunohistochemistry of placental tissues and differentiating villous explant cultures showed that expression of TCF-3/4 strongly increased in invading trophoblasts. Some of these cells also accumulated dephosphorylated ß-catenin in the nucleus. Wnt3A treatment of primary cytotrophoblasts and SGHPL-5 cells induced activity of TCF-luciferase reporters. Accordingly, the ligand provoked interaction of TCF-3/4 with ß-catenin as assessed in electrophoretic mobility shift assays (EMSAs) and up-regulation of Wnt/TCF target genes as observed by Western blot analyses. Wnt3A stimulated trophoblast migration and invasion through Matrigel, which could be blocked by addition of Dickkopf-1, mediating in-hibition of canonical Wnt signaling. Dickkopf-1 also reduced basal migration, invasion, and proliferation of cytotrophoblasts, suggesting expression of endogenous Wnt ligand(s). Immunohistochemistry revealed that the percentage of extravillous trophoblasts containing nuclear ß-catenin was significantly higher in placentas of complete hydatidiform mole pregnancies as compared to normal placentas. Thus, canonical Wnt signaling may promote invasive trophoblast differentiation, and exaggerated activation of the path-way could contribute to trophoblastic hyperplasia and local invasion.
This article has been cited by other articles:
 |
|
 |
|
  S. Sonderegger, P. Haslinger, A. Sabri, C. Leisser, J. V. Otten, C. Fiala, and M. Knofler Wingless (Wnt)-3A Induces Trophoblast Migration and Matrix Metalloproteinase-2 Secretion through Canonical Wnt Signaling and Protein Kinase B/AKT Activation Endocrinology, January 1, 2010; 151(1): 211 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. G. Holtan, D. J. Creedon, P. Haluska, and S. N. Markovic Cancer and Pregnancy: Parallels in Growth, Invasion, and Immune Modulation and Implications for Cancer Therapeutic Agents Mayo Clin. Proc., November 1, 2009; 84(11): 985 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, D. W. Erikson, S. A. Tilford, B. M. Bany, J. A. Maclean II, E. B. Rucker III, G. A. Johnson, and T. E. Spencer Wnt Genes in the Mouse Uterus: Potential Regulation of Implantation Biol Reprod, May 1, 2009; 80(5): 989 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Bilban, P. Haslinger, J. Prast, F. Klinglmuller, T. Woelfel, S. Haider, A. Sachs, L. E. Otterbein, G. Desoye, U. Hiden, et al. Identification of Novel Trophoblast Invasion-Related Genes: Heme Oxygenase-1 Controls Motility via Peroxisome Proliferator-Activated Receptor {gamma} Endocrinology, February 1, 2009; 150(2): 1000 - 1013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Mikheev, T. Nabekura, A. Kaddoumi, T. K. Bammler, R. Govindarajan, M. F. Hebert, and J. D. Unadkat Profiling Gene Expression in Human Placentae of Different Gestational Ages: An OPRU* Network and UW SCOR Study Reproductive Sciences, November 1, 2008; 15(9): 866 - 877. [Abstract] [PDF]
|
|
|
|
 |
|
 B. Novakovic, V. Rakyan, H.K. Ng, U. Manuelpillai, C. Dewi, N.C. Wong, R. Morley, T. Down, S. Beck, J.M. Craig, et al. Specific tumour-associated methylation in normal human term placenta and first-trimester cytotrophoblasts Mol. Hum. Reprod., September 1, 2008; 14(9): 547 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. LaMarca, P. R. Dash, K. Vishnuthevan, E. Harvey, D. E. Sullivan, C. A. Morris, and G. St. J. Whitley Epidermal growth factor-stimulated extravillous cytotrophoblast motility is mediated by the activation of PI3-K, Akt and both p38 and p42/44 mitogen-activated protein kinases Hum. Reprod., August 1, 2008; 23(8): 1733 - 1741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Prast, L. Saleh, H. Husslein, S. Sonderegger, H. Helmer, and M. Knofler Human Chorionic Gonadotropin Stimulates Trophoblast Invasion through Extracellularly Regulated Kinase and AKT Signaling Endocrinology, March 1, 2008; 149(3): 979 - 987. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Hayashi, R. C. Burghardt, F. W. Bazer, and T. E. Spencer WNTs in the Ovine Uterus: Potential Regulation of Periimplantation Ovine Conceptus Development Endocrinology, July 1, 2007; 148(7): 3496 - 3506. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
