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Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue

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  • Neha Diwanji

    (Department of Molecular, Cell and Cancer Biology)

  • Andreas Bergmann

    (Department of Molecular, Cell and Cancer Biology)

Abstract

Macrophages are a major immune cell type infiltrating tumors and promoting tumor growth and metastasis. To elucidate the mechanism of macrophage recruitment, we utilize an overgrowth tumor model (“undead” model) in larval Drosophila imaginal discs that are attached by numerous macrophages. Here we report that changes to the microenvironment of the overgrown tissue are important for recruiting macrophages. First, we describe a correlation between generation of reactive oxygen species (ROS) and damage of the basement membrane (BM) in all neoplastic, but not hyperplastic, models examined. ROS and the stress kinase JNK mediate the accumulation of matrix metalloproteinase 2 (Mmp2), damaging the BM, which recruits macrophages to the tissue. We propose a model where macrophage recruitment to and activation at overgrowing tissue is a multi-step process requiring ROS- and JNK-mediated Mmp2 upregulation and BM damage. These findings have implications for understanding the role of the tumor microenvironment for macrophage activation.

Suggested Citation

  • Neha Diwanji & Andreas Bergmann, 2020. "Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17399-8
    DOI: 10.1038/s41467-020-17399-8
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    Cited by:

    1. Stefan Harmansa & Alexander Erlich & Christophe Eloy & Giuseppe Zurlo & Thomas Lecuit, 2023. "Growth anisotropy of the extracellular matrix shapes a developing organ," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Julian C. Bahr & Xiao-Yan Li & Tamar Y. Feinberg & Long Jiang & Stephen J. Weiss, 2022. "Divergent regulation of basement membrane trafficking by human macrophages and cancer cells," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

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