Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling

Sunyoung Ham, Luize G. Lima, Edna Pei Zhi Chai, Alexandra Muller, Richard J. Lobb, Sophie Krumeich, Shu Wen Wen, Adrian P. Wiegmans, Andreas Möller

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132 Citations (Scopus)


Tumor-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 tumor-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 macrophages through the interleukin-6 (IL-6) receptor beta (glycoprotein 130, gp130)-STAT3 signaling 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 toward a polarized phenotype often observed in tumor-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 signaling.

Original languageEnglish
Article number871
Number of pages10
JournalFrontiers in Immunology
Issue numberMAY
Publication statusPublished - 8 May 2018


  • Breast cancer
  • Cancer-derived exosomes
  • Glycoprotein 130
  • Interleukin-6
  • STAT3
  • Tumor-associated macrophages

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