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.
