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Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype

Author

Listed:
  • Ann-Christin Frank

    (Goethe-University Frankfurt)

  • Stefanie Ebersberger

    (Institute of Molecular Biology gGmbH)

  • Annika F. Fink

    (Goethe-University Frankfurt)

  • Sebastian Lampe

    (Goethe-University Frankfurt)

  • Andreas Weigert

    (Goethe-University Frankfurt)

  • Tobias Schmid

    (Goethe-University Frankfurt)

  • Ingo Ebersberger

    (Institute for Cell Biology and Neuroscience, Goethe-University Frankfurt
    Senckenberg Biodiversity and Climate Research Centre Frankfurt (BIK-F))

  • Shahzad Nawaz Syed

    (Goethe-University Frankfurt)

  • Bernhard Brüne

    (Goethe-University Frankfurt
    German Cancer Research Consortium (DKTK), Partner Site)

Abstract

Tumor-immune cell interactions shape the immune cell phenotype, with microRNAs (miRs) being crucial components of this crosstalk. How they are transferred and how they affect their target landscape, especially in tumor-associated macrophages (TAMs), is largely unknown. Here we report that breast cancer cells have a high constitutive expression of miR-375, which is released as a non-exosome entity during apoptosis. Deep sequencing of the miRome pointed to enhanced accumulation of miR-375 in TAMs, facilitated by the uptake of tumor-derived miR-375 via CD36. In macrophages, miR-375 directly targets TNS3 and PXN to enhance macrophage migration and infiltration into tumor spheroids and in tumors of a xenograft mouse model. In tumor cells, miR-375 regulates CCL2 expression to increase recruitment of macrophages. Our study provides evidence for miR transfer from tumor cells to TAMs and identifies miR-375 as a crucial regulator of phagocyte infiltration and the subsequent development of a tumor-promoting microenvironment.

Suggested Citation

  • Ann-Christin Frank & Stefanie Ebersberger & Annika F. Fink & Sebastian Lampe & Andreas Weigert & Tobias Schmid & Ingo Ebersberger & Shahzad Nawaz Syed & Bernhard Brüne, 2019. "Apoptotic tumor cell-derived microRNA-375 uses CD36 to alter the tumor-associated macrophage phenotype," Nature Communications, Nature, vol. 10(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08989-2
    DOI: 10.1038/s41467-019-08989-2
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    Cited by:

    1. Antonio Citro & Alessia Neroni & Cataldo Pignatelli & Francesco Campo & Martina Policardi & Matteo Monieri & Silvia Pellegrini & Erica Dugnani & Fabio Manenti & Maria Chiara Maffia & Libera Valla & El, 2023. "Directed self-assembly of a xenogeneic vascularized endocrine pancreas for type 1 diabetes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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