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

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

Abstract

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
Volume9
Issue numberMAY
DOIs
Publication statusPublished - 8 May 2018

Keywords

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

Cite this

Ham, S., Lima, L. G., Chai, E. P. Z., Muller, A., Lobb, R. J., Krumeich, S., ... Möller, A. (2018). Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling. Frontiers in Immunology, 9(MAY), [871]. https://doi.org/10.3389/fimmu.2018.00871
Ham, Sunyoung ; Lima, Luize G. ; Chai, Edna Pei Zhi ; Muller, Alexandra ; Lobb, Richard J. ; Krumeich, Sophie ; Wen, Shu Wen ; Wiegmans, Adrian P. ; Möller, Andreas. / Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling. In: Frontiers in Immunology. 2018 ; Vol. 9, No. MAY.
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Ham, S, Lima, LG, Chai, EPZ, Muller, A, Lobb, RJ, Krumeich, S, Wen, SW, Wiegmans, AP & Möller, A 2018, 'Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling', Frontiers in Immunology, vol. 9, no. MAY, 871. https://doi.org/10.3389/fimmu.2018.00871

Breast cancer-derived exosomes alter macrophage polarization via gp130/STAT3 signaling. / Ham, Sunyoung; Lima, Luize G.; Chai, Edna Pei Zhi; Muller, Alexandra; Lobb, Richard J.; Krumeich, Sophie; Wen, Shu Wen; Wiegmans, Adrian P.; Möller, Andreas.

In: Frontiers in Immunology, Vol. 9, No. MAY, 871, 08.05.2018.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Wiegmans, Adrian P.

AU - Möller, Andreas

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