Unraveling mural cell-like macrophages: a new approach for regulating tumor vasculature 9298

Description Tumor-associated macrophages are indispensable in the modulation of tumor angiogenesis, and their role in normalizing tumor vasculature is attracting current interest. We have recently discovered that macrophages position themselves perivascularly in injured, ischemic muscle, and that this is important for healing of the ischemic injury as they can take on mural cell functions including vessel maturation, as well as mural cell gene expression while losing their macrophage identity. The aim of the current study is to determine the importance of the mural cell-like macrophages for tumor vasculature. A murine model of breast cancer was used, where EO771 cells are injected into the mammary gland to induce tumor growth. To enable lineage tracing of macrophages in the tumor environment, Cx3cr1CreERT2xRosa26-TdTomato mice crossed with PdgfrβeGFP reporter mice was used, resulting in TdTomato expression in CX3CR1+ macrophages following tamoxifen administration. The presence of PDGFRβ-positive macrophages in the tumor microenvironment was confirmed using flow cytometry of tumor single-cell suspensions. Immunofluorescence of tumor sections demonstrated that these macrophages position themselves perivascularly. In conclusion, mural-cell-like macrophages are present in growing murine mammary tumors, and their role in the maturation of tumor vasculature is now being explored to understand the therapeutic potential of these cells. Funding Sources Research Council (K2012-99x, 65X-12219-15-6, 5570x-15043, O4X-08646, K2015-54X-12219-19-4), Ragnar Söderberg foundation, Knut and Alice Wallenberg foundation, Swedish Foundation for Strategic Research, Diabetes Wellness Sweden, The Swedish Cancer Society Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)