Abstract
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.
Highlights
The tumour microenvironment is a key regulators of tumour progression through the secretion of growth factors that activate epithelial-mesenchymal transition (EMT)
Our results demonstrate the potential for human adipocytes to enhance proliferation, migration and invasion abilities of MDA-MB-468 and MCF-7 cells after co-culture
We examined the expression of Epithelial-mesenchymal transition (EMT)-TFs (SNAIL and twist basic helix-loop-helix transcription factor (TWIST)) and EMT-related genes (E-cadherin, N-cadherin and matrix metalloprotease 9 (MMP9)) in breast cancer cells co-cultured with adipocytes by quantitative real time PCR
Summary
The tumour microenvironment is a key regulators of tumour progression through the secretion of growth factors that activate epithelial-mesenchymal transition (EMT). We hypothesized that paracrine signalling by adipocytes can activate EMT and results in increased migration and invasion characteristics of breast cancer cells. 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. The secretion of hormones, growth factors and cytokines (collectively referred to as adipocytokines) by adipocytes have been hypothesized to activate various signalling pathways in the nearby tumour cells resulting in increased migration and invasion in breast cancer cells[16]. We found that adipocytes enhanced proliferation, migration and invasion characteristics of breast cancer cells with the emergence of an EMT phenotype. Our data demonstrates that human adipocytes can enhance the proliferation, invasion and migration characteristics of breast cancer cells and induce an EMT phenotype through paracrine IL-6/STAT3 signalling
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