Signal Transducer and Activator of Transcription 3 (STAT3) and Trophoblast Invasion

Journal für Reproduktionsmedizin und Endokrinologie - Journal of Reproductive Medicine and Endocrinology 2007; 4 (6): 322-330

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Keywords: Reproduktionsmedizin,  Throphoblast,  reproductive medicine,  throphoblast cells,  throphoblast invasion

Human trophoblast cells have the fascinating property of physiological invasiveness into allogenic tissue. The underlying mechanisms, such as extra- and intracellular signalling, are very similar to those abused by a variety of tumours. The main contrasting feature to cancerous cells is the very fundamental ability of trophoblasts to auto-regulate invasion with respect to time and space. Trophoblast cells start invasion into the decidua very shortly after implantation, which approaches a maximum during the first trimester of gestation period. During this period of time, several cytokines from cells of different maternal origin, including NK cells, dendritic cells, stroma cells and endothelial cells, are present which, analogous to the situation in tumours, have the potential to trigger and enhance invasion, migration and proliferation of trophoblast cells. These mainly include interleukin-6 (IL-6), IL-11, Leukaemia Inhibitory Factor (LIF), Hepatocyte Growth Factor (HGF) and Insulin-like Growth Factors (IGF). Cytokines, upon binding to their specific receptors present on the trophoblast cells, trigger several intracellular signalling cascades. One of these signalling pathways is the Janus Kinase (Jak)/Signal Transducers and Activators of Transcription (STAT) pathway. As recent studies have shown, the tyrosine phosphorylated form of STAT3 is a major inducer of invasiveness which mainly takes place upon binding of LIF to its receptor. For autoregulation of signals, STAT3 induces the transcription of Suppressor of Cytokine Signalling 3 (SOCS3). The balance between STAT3 and SOCS3 may be argued as one of the main tuners of trophoblast invasion for successful implantation. Disturbances in this balance may lead to serious complications like cancer and implantation failure.