Oral Presentation Australasian Extracellular Vesicles Conference 2018

Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling (#7)

Sunyoung Ham 1 2 , Luize Lima 1 , Andreas Moller 1 2 3
  1. Tumour Microenvironment laboratory, Qimr berghofer medical institute, Herston, QUEENSLAND, Australia
  2. School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia
  3. Faculty of Medicine, University of Queensland, Brisbane, QLD, Australia

Tumour-derived exosomes are being recognized as essential mediators of intercellular communication between cancer and immune cells. It is well established that bone marrow-derived macrophages (BMDMs) take up tumour-derived exosomes. However, the functional impact of these exosomes on macrophage phenotypes is controversial and not well studied. Here, we show that breast cancer-derived exosomes alter the phenotype of BMDMs through the Interleukin 6 (IL-6) receptor beta (glycoprotein 130, gp130)-STAT3 signalling pathway. Addition of breast cancer-derived exosomes to macrophages results in the activation of the IL-6 response pathway, including phosphorylation of the key downstream transcription factor STAT3. Exosomal gp130, which is highly enriched in cancer exosomes, triggers the secretion of IL-6 from BMDMs. Moreover, the exposure of BMDMs to cancer-derived exosomes triggers changes from a conventional towards a polarized phenotype often observed in tumour-associated macrophages. All of these effects can be inhibited through the addition of a gp130 inhibitor to cancer-derived exosomes or by blocking BMDMs exosome uptake. Collectively, this work demonstrates that breast cancer derived-exosomes are capable of inducing IL-6 secretion and a pro-survival phenotype in macrophages, partially via gp130/STAT3 signalling.