Poster Presentation Australasia Extracellular Vesicles Conference 2017

Breast cancer-derived exosomes cause macrophage polarisation towards an TAM phenotype (#50)

Sunyoung Ham 1 2 , Andreas Moller 2 , Luize Lima 2
  1. Queensland University of Technology, Herston, QUEENSLAND, Australia
  2. Tumour Microenvironment laboratory, Qimr berghofer medical institute, Herston, QUEENSLAND, Australia

Tumour derived-exosomes are being recognized as essential intermediary of intercellular communication between cancer and immune cells. macrophages are well established to take up tumour-derived exosomes, however, the functional impact of these exosomes on Bone marrow derived-macrophages (BMDM) phenotypes is controversial. Here, we show that breast cancer derived-exosomes affect macrophage phenotypes through Interleukin 6 (IL-6) receptor β (GP130) - STAT3 signal pathways. Exosomes collected from syngeneic mouse breast cancer cell lines were analysed for their abundance, morphology and size distribution. Using proteomic approaches, we found that these breast cancer-derived exosomes are containing a high abundance of the GP130. Addition of the breast cancer-derived exosomes to murine macrophages results in the activation of the IL-6 response pathway, including phosphorylation of the key downstream transcription factor STAT3. Exosomal GP130 furthermore triggers the secretion of IL6 from these macrophages. All of these effects can be inhibited through the addition of a GP130 inhibitor to the cancer-derived exosomes or by blocking of exosome uptake. Additionally, the exposure of macrophages to cancer-derived exosomes triggers phenotypical changes from the conventional (M1) macrophage to a more tumour-associated, or M2, macrophage feature. Together, this work demonstrates that breast cancer derived-exosomes are capable, partially via GP130/STAT3 signalling, to alter the macrophages polarisation into a tumour promoting TAM phenotype.