Metastasis-associated macrophages (MAMs) at metastatic sites induce angiogenesis and tumor growth, partially through production of the angiogenic factor VEGF. In the Journal of Experimental Medicine, Qian et al. show that expression of Flt1, a VEGF receptor, promotes tumor metastasis by regulating the expression of a set of pro-inflammatory genes in MAMs. Human breast tumor metastases show significant enrichment for Flt1+ macrophages compared with their abundance in primary tumors. Flt1 signaling in macrophages is required for the formation of metastatic tumors in mice but not for the recruitment or extravasation of MAMs to the metastatic site. Ly6c+ inflammatory monocytes, the precursors of MAMs, do not express Flt1. Among the Flt1-dependent pro-inflammatory gene signature in MAMs, expression of the gene encoding the macrophage survival factor CSF1 is required for efficient tumor metastasis. Thus, specific expression of Flt1 on MAMs creates an inflammatory environment that allows metastatic growth after seeding.

J. Exp. Med. (10 August 2015) doi:10.1084/jem.20141555