Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells

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Extravillous trophoblast cells resemble cancer cells with regard to their intrinsic invasiveness. They invade decidual tissue, but, unlike tumor cells, shut down their invasive properties, when they become inappropriate. Stimuli involved in the modulation of invasion, as well as their underlying signaling mechanisms require further clarification. We were especially interested in discovering signals capable of stimulating invasion in otherwise low-invasive cells involved in reproduction. Using the choriocarcinoma cell line Jeg-3 as a model, we have addressed the potential role of cytokine/growth factor-driven activation of signal transducer and activator of transcription 3 (STAT3) in this process. Jeg-3 cells were treated with various factors known to induce trophoblast proliferation, differentiation, migration, or invasiveness (insulin-like-growth-factor-II (IGF-II), hepatocyte growth factor (HGF), interleukin-6 (IL-6), and leukemia inhibitory factor (LIF)). Only LIF elicited strong tyrosine phosphorylation and specific DNA-binding activity of STAT3. It induced a significant acceleration of cell proliferation and promoted the capability of Jeg-3 cells to invade into an artificial extracellular matrix. Moreover, LIF influenced the expression pattern of proteases and protease inhibitors with potential relevance for invasiveness (downregulation of mRNA for tissue inhibitor of metalloproteinase 1 (TIMP-1) and upregulation of mRNA for caspase-4). In conjunction with earlier work, in which we found that STAT3 DNA-binding activity was increased in invasive cells (choriocarcinoma, first trimester trophoblasts) and absent in non-invasive cells (term trophoblasts), these findings suggest a connection between LIF-driven STAT3 activity and invasiveness of choriocarcinoma and trophoblast cells.


  • Justine S. Fitzgerald
  • Svetlana A. Tsareva
  • Tobias G. Poehlmann
  • Luciana Berod
  • Anja Meissner
  • Florian M. Corvinus
  • Bernd Wiederanders
  • Edith Pfitzner
  • Udo R. Markert
  • Karlheinz Friedrich
External organisations
  • Friedrich Schiller University Jena
  • Institute of Humoral Immunity Study (IDEHU)
  • Georg Speyer Haus - Institute for Tumor biology and Experimental Therapy
Research areas and keywords


  • Choriocarcinoma, Invasion, LIF, STAT3, Trophoblast
Original languageEnglish
Pages (from-to)2284-2296
Number of pages13
JournalInternational Journal of Biochemistry and Cell Biology
Issue number11
Publication statusPublished - 2005 Nov
Publication categoryResearch
Externally publishedYes