Interleukin-11 increases invasiveness of JEG-3 choriocarcinoma cells by modulating STAT3 expression.
Amongst the interleukin-6 (IL-6) family of cytokines, leukemia inhibitory factor (LIF) has been shown to promote trophoblast invasion and proliferation. In the present study interleukin-11 (IL-11), another member of the IL-6 family, was investigated for its role in regulating invasion, migration and proliferation of JEG-3 choriocarcinoma cells. JEG-3 cells, like extra villous trophoblast (EVT), express mRNA transcripts encoding IL-11 and IL-11 receptor-alpha (IL-11Ralpha). Treatment of JEG-3 cells with IL-11 led to an increase in invasion across Matrigel extracellular matrix without an increase in proliferation. There was a dose-dependent increase in activation of STAT3 under the influence of IL-11 with maximum Tyr705 phosphorylation by 10min. In addition, treatment of JEG-3 cells with IL-11 for 24h led to an increase in expression of unphosphorylated STAT1 and STAT3. Analysis of the nuclear fraction showed an increased localization of STAT3 following IL-11 treatment while STAT1 was absent. Silencing the expression of STAT3 by siRNA caused a 25% reduction in invasion compared to control cells, however this was not significant. Furthermore, treatment of STAT3-silenced JEG-3 cells with IL-11 led to a significant increase in invasion compared to STAT3-silenced cells without cytokine, but this was not significant compared to non-transfected control cells. Silencing the expression of gp130 but not of IL-6R abrogated the increase in invasiveness of JEG-3 cells following IL-11 treatment. In conclusion, activation and upregulation of STAT3 appears to be critical for the IL-11-mediated increase in invasiveness of JEG-3 cells.
Suman
Pankaj
P
National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi, India.
Poehlmann
Tobias G
TG
Prakash
Golla Jaya
GJ
Markert
Udo R
UR
Gupta
Satish K
SK
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002822:Choriocarcinoma / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D050822:Cytokine Receptor gp130 / Q000235:genetics; D005260:Female; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D017370:Interleukin-11 / Q000494:pharmacology*; D009361:Neoplasm Invasiveness / Q000276:immunology; D011247:Pregnancy; D034741:RNA, Small Interfering / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D014594:Uterine Neoplasms / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D017370:Interleukin-11; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D050822:Cytokine Receptor gp130