Title |
Macrophages orchestrate breast cancer early dissemination and metastasis
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Published in |
Nature Communications, January 2018
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DOI | 10.1038/s41467-017-02481-5 |
Pubmed ID | |
Authors |
Nina Linde, Maria Casanova-Acebes, Maria Soledad Sosa, Arthur Mortha, Adeeb Rahman, Eduardo Farias, Kathryn Harper, Ethan Tardio, Ivan Reyes Torres, Joan Jones, John Condeelis, Miriam Merad, Julio A. Aguirre-Ghiso |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 24 | 27% |
Spain | 5 | 6% |
Mexico | 4 | 4% |
France | 2 | 2% |
Italy | 2 | 2% |
Canada | 2 | 2% |
Belgium | 2 | 2% |
Austria | 1 | 1% |
Iraq | 1 | 1% |
Other | 7 | 8% |
Unknown | 39 | 44% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 57 | 64% |
Scientists | 27 | 30% |
Science communicators (journalists, bloggers, editors) | 5 | 6% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 470 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 116 | 25% |
Researcher | 80 | 17% |
Student > Master | 45 | 10% |
Student > Bachelor | 33 | 7% |
Student > Doctoral Student | 26 | 6% |
Other | 61 | 13% |
Unknown | 109 | 23% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 104 | 22% |
Agricultural and Biological Sciences | 69 | 15% |
Immunology and Microbiology | 50 | 11% |
Medicine and Dentistry | 50 | 11% |
Engineering | 20 | 4% |
Other | 45 | 10% |
Unknown | 132 | 28% |