Macrophages orchestrate breast cancer early dissemination and metastasis.
Macrophages orchestrate breast cancer early dissemination and metastasis.
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DOI：
10.1038/s41467-017-02481-5
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发表时间：
2018-01-02
影响因子：
16.6
通讯作者：
Aguirre-Ghiso JA
中科院分区：
文献类型：
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作者：
Linde N;Casanova-Acebes M;Sosa MS;Mortha A;Rahman A;Farias E;Harper K;Tardio E;Reyes Torres I;Jones J;Condeelis J;Merad M;Aguirre-Ghiso JA
在乳腺癌的非常早期阶段，癌细胞的传播通过知之甚少的机制进行。在这里，我们表明，在HER 2+乳腺癌的小鼠模型中，先前描述的早期进化的癌细胞亚群需要巨噬细胞进行早期传播。特别是在癌前阶段期间巨噬细胞的消耗减少了早期传播，并且还导致在癌症进展的终末期转移负荷降低。从机制上讲，我们表明，在癌前病变中，癌细胞和骨髓细胞产生的CCL 2吸引CD 206 +/Tie 2+巨噬细胞，并诱导Wnt-1上调，进而下调HER 2+早期癌细胞中的E-钙粘蛋白连接。我们还观察了癌前病变转移结构中含有巨噬细胞的肿瘤微环境，这些微环境可以作为血管内渗的门户。这些数据支持巨噬细胞在早期传播中的因果作用，其影响癌症进展中的长期转移发展。对人体标本的初步分析显示，原位导管癌中存在上皮内巨噬细胞和E-钙粘蛋白连接丢失，支持潜在的临床相关性。据报道，在某些乳腺癌模型中发生了癌细胞的早期扩散。在这里，作者表明，早期癌前病变中的上皮内巨噬细胞通过Wnt-1分泌驱动早期癌细胞传播，并且这些事件影响转移的后期发展。
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. Early dissemination of cancer cells has been reported to occur in certain breast cancer models. Here the authors show that intra-epithelial macrophages in the early pre-cancer lesions drive early cancer cell dissemination through Wnt-1 secretion and that such events impact the later development of metastasis.
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影响因子：
3.7
作者：
Cosín-Roger J;Ortiz-Masiá D;Calatayud S;Hernández C;Alvarez A;Hinojosa J;Esplugues JV;Barrachina MD
通讯作者：
Barrachina MD
影响因子：
6
作者：
Lederle, Wiltrud;Linde, Nina;Mueller, Margareta M.
通讯作者：
Mueller, Margareta M.
影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
影响因子：
15.9
作者：
Eyles, Jo;Puaux, Anne-Laure;Abastado, Jean-Pierre
通讯作者：
Abastado, Jean-Pierre
肿瘤相关巨噬细胞的细胞和分子起源。
DOI：
10.1126/science.1252510
发表时间：
2014-05-23
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Franklin RA;Liao W;Sarkar A;Kim MV;Bivona MR;Liu K;Pamer EG;Li MO
通讯作者：
Li MO