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

Diwanji, Neha; Bergmann, Andreas ✉

Angol nyelvű Tudományos Szakcikk (Folyóiratcikk)
Megjelent: NATURE COMMUNICATIONS 2041-1723 11 (1) Paper: 3631 , 14 p. 2020
  • SJR Scopus - Biochemistry, Genetics and Molecular Biology (miscellaneous): D1
    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. The molecular mechanisms regulating macrophage recruitment to tumors are unclear. Here, the authors use a Drosophila overgrowth model to show how damaged basement membranes recruit macrophages to undead tissue, via an interdependent effect of reactive oxygen species and matrix metalloproteinase 2.
    Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
    2021-03-02 12:13