STAT3 activation by IL-6 from adipose-derived stem cells promotes endometrial carcinoma proliferation and metastasis

Biochem Biophys Res Commun. 2018 Jun 7;500(3):626-631. doi: 10.1016/j.bbrc.2018.04.121. Epub 2018 Apr 24.

Abstract

Endometrial cancer is the most common gynaecological cancer, and its incidence is increasing. Obesity is a well-recognized risk factor for endometrial cancer, and the mechanisms by which adipose tissue influences tumour development remain controversial. In this study, we examined the high IL-6 level in the ADSCs supernatant following treatment of endometrial cancer cell CM. Then, the activation of STAT3, a major tumourigenic IL-6 effector, was examined in ADSCs CM treated endometrial cancer cells. Conditioned ADSC medium was used to stimulate endometrial cancer cell growth in vitro. Similar to IL-6, ADSC-conditioned medium significantly promoted endometrial cancer growth and invasion. Furthermore, siRNA-mediated STAT3 inhibition in endometrial cancer cells decreased the ADSC-mediated promotion of cell proliferation and invasion. In addition, a subcutaneous nude mouse model of endometrial cancer was established to monitor the tumour-promoting effect of ADSCs. ADSC-conditioned medium promoted tumour growth, and STAT3 inhibition attenuated this effect. Based on these data, ADSCs promote endometrial cancer progression by the STAT3 signalling pathway.

Keywords: Adipose-derived mesenchymal stem cells; Endometrial carcinoma; Metastasis; Proliferation; STAT3 pathway.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Endometrial Neoplasms / pathology*
  • Female
  • Humans
  • Interleukin-6 / metabolism*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • STAT3 Transcription Factor / metabolism*
  • Stem Cells / cytology*

Substances

  • Interleukin-6
  • STAT3 Transcription Factor