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

Nature Communications
Neha Diwanji, Andreas Bergmann

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.

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Citations

Aug 15, 2021·Nature Reviews. Cancer·David BilderJung Kim
Aug 28, 2021·International Journal of Molecular Sciences·Caroline DillardTor Erik Rusten
Aug 28, 2021·International Journal of Molecular Sciences·Caitlin Hounsell, Yun Fan
Nov 16, 2021·Archives of Insect Biochemistry and Physiology·Banani BindhaniSamir Kumar Saha

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Methods Mentioned

BETA
transmission electron microscopy
transgenic
zymography
confocal microscopy
Assay
PCR
Fluorescence

Software Mentioned

ImageJ
GraphPad Prism
Zen
Adobe Photoshop

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