The tumour microenvironment is a key regulators of tumour progression through the secretion of growth factors that activate epithelial-mesenchymal transition (EMT). Induction of EMT is a key step for transition from a benign state to a metastatic tumour. Adipose tissue forms a bulk portion of the breast cancer microenvironment, emerging evidence indicates the potential for adipocytes to influence tumour progression through the secretion of adipokines that can induce EMT. The molecular mechanisms underlying how adipocytes enhance breast cancer progression is largely unknown. We hypothesized that paracrine signalling by adipocytes can activate EMT and results in increased migration and invasion characteristics of breast cancer cells. We found that IL-6 secreted by adipocytes induce EMT in breast cancer cells. The effect of IL-6 expression on EMT is mediated through activation of the signal transducer and activated of transcription 3 (STAT3). Blocking of IL-6 signalling in breast cancer cells and adipocytes, decreased proliferation, migration and invasion capabilities and altered the expression of genes regulating EMT. Together, our results suggest that matured human adipocytes can enhance the aggressive behaviour of breast cancer cells and induce an EMT-phenotype through paracrine IL-6/STAT3 signalling.
Bibliographical noteFunding Information:
The authors thank Haerin Jang and Juwon Kang of the Laboratory of Translational cancer research, Yonsei University for their generous assistance. This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF 2014R1A1A1002443, 2016M3C7A1913844, NRF 2017R1D1A1B03033362 and NRF 2018R1A6A1A03023718) and the Faculty research grant of Yonsei University, Wonju College of Medicine.
© 2018 The Author(s).
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