2026-04-29T19:34:57Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/272612026-02-23T01:16:30Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Linde, Nina author Casanova-Acebes, Maria author Sosa, Maria Soledad author Mortha, Arthur author Rahman, Adeeb author Farias, Eduardo author Harper, Kathryn author Tardio, Ethan author Reyes Torres, Ivan author Jones, Joan author Condeelis, John author Merad, Miriam author Aguirre-Ghiso, Julio A author 2018-01-02 Cancer cell dissemination during very early stages of breast cancer proceeds through poorly understood mechanisms. Here we show, in a mouse model of HER2 breast cancer, that a previously described sub-population of early-evolved cancer cells requires macrophages for early dissemination. Depletion of macrophages specifically during pre-malignant stages reduces early dissemination and also results in reduced metastatic burden at end stages of cancer progression. Mechanistically, we show that, in pre-malignant lesions, CCL2 produced by cancer cells and myeloid cells attracts CD206/Tie2 macrophages and induces Wnt-1 upregulation that in turn downregulates E-cadherin junctions in the HER2 early cancer cells. We also observe macrophage-containing tumor microenvironments of metastasis structures in the pre-malignant lesions that can operate as portals for intravasation. These data support a causal role for macrophages in early dissemination that affects long-term metastasis development much later in cancer progression. A pilot analysis on human specimens revealed intra-epithelial macrophages and loss of E-cadherin junctions in ductal carcinoma in situ, supporting a potential clinical relevance. Nat Commun . 2018 Jan 2;9(1):21. Nature Communications 29295986 https://hdl.handle.net/20.500.12105/27261 CARCINOMA IN-SITU COLONY-STIMULATING FACTOR DISSEMINATED TUMOR-CELLS MAMMARY-GLAND BONE-MARROW PHENOTYPIC HETEROGENEITY EXPRESSION MIGRATION RADIOTHERAPY ACTIVATION Macrophages orchestrate breast cancer early dissemination and metastasis.