Department of Molecular, Cell and Cancer Biology
Amino Acids, Peptides, and Proteins | Cancer Biology | Cell Biology | Cellular and Molecular Physiology | Enzymes and Coenzymes | Hemic and Immune Systems | Molecular Biology
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.
Apicobasal polarity, Apoptosis, Extracellular signalling molecules, Stress signalling
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DOI of Published Version
Diwanji N, Bergmann A. Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue. Nat Commun. 2020 Jul 20;11(1):3631. doi: 10.1038/s41467-020-17399-8. PMID: 32686670; PMCID: PMC7371875. Link to article on publisher's site
Diwanji N, Bergmann A. (2020). Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue. Open Access Articles. https://doi.org/10.1038/s41467-020-17399-8. Retrieved from https://escholarship.umassmed.edu/oapubs/4299
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This work is licensed under a Creative Commons Attribution 4.0 License.
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