Characterization of macrophage--cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer.
Characterization of macrophage--cancer cell crosstalk in estrogen receptor positive and triple-negative breast cancer.
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DOI：
10.1038/srep09188
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发表时间：
2015-03-17
影响因子：
4.6
通讯作者：
Detmar M
中科院分区：
文献类型：
--
作者：
Hollmén M;Roudnicky F;Karaman S;Detmar M
肿瘤异质性可能广泛影响肿瘤相关巨噬细胞的活化。我们的目的是剖析不同分子特征的乳腺癌细胞如何影响巨噬细胞的表型和功能。因此，我们对与雌激素受体阳性（ER+）或三阴性（TNBC）乳腺癌细胞系共培养的人单核细胞进行了全转录组测序，并通过通路分析研究了单核细胞和癌细胞中与差异基因激活相关的生物学反应。ER+和TNBC癌细胞系诱导具有不同生物学功能、细胞因子和趋化因子分泌以及形态的明显不同的巨噬细胞表型。相反，ER+和TNBC乳腺癌细胞系明显受到巨噬细胞存在的影响。ER+细胞表现出急性期炎症反应、IL-17信号传导和抗原呈递途径的上调，而硫氧还蛋白和维生素D3受体途径在相应的巨噬细胞中下调。TNBC培养的巨噬细胞下调瓜氨酸代谢，并分化为M2样巨噬细胞，MMR蛋白表达和CCL 2分泌增加。这些数据证明了不同的癌细胞如何教育宿主细胞以支持肿瘤生长，并可能解释为什么TNBC肿瘤中巨噬细胞的高浸润与预后不良相关。
Tumor heterogeneity may broadly influence the activation of tumor-associated macrophages. We aimed to dissect how breast cancer cells of different molecular characteristics contribute to macrophage phenotype and function. Therefore, we performed whole transcriptome sequencing of human monocytes that were co-cultured with estrogen receptor positive (ER+) or triple-negative (TNBC) breast cancer cell lines and studied the biological responses related to the differential gene activation in both monocytes and cancer cells by pathway analysis. ER+ and TNBC cancer cell lines induced distinctly different macrophage phenotypes with different biological functions, cytokine and chemokine secretion, and morphology. Conversely, ER+ and TNBC breast cancer cell lines were distinctly influenced by the presence of macrophages. ER+ cells demonstrated up-regulation of an acute phase inflammatory response, IL-17 signaling and antigen presentation pathway, whereas thioredoxin and vitamin D3 receptor pathways were down-regulated in the respective macrophages. The TNBC educated macrophages down-regulated citrulline metabolism and differentiated into M2-like macrophages with increased MMR protein expression and CCL2 secretion. These data demonstrate how different cancer cells educate the host cells to support tumor growth and might explain why high infiltration of macrophages in TNBC tumors associates with poor prognosis.
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影响因子：
2.6
作者：
Hanada, T;Nakagawa, M;Nomura, Y
通讯作者：
Nomura, Y
影响因子：
4.8
作者：
Loberg, Robert D.;Ying, Chi;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.
DOI：
10.1016/j.jamcollsurg.2013.02.025
发表时间：
2013-07-01
影响因子：
5.2
作者：
Li, Neill Y.;Weber, Cynthia E.;Kuo, Paul C.
通讯作者：
Kuo, Paul C.
影响因子：
3
作者：
Kim KI;van de Wiel MA
通讯作者：
van de Wiel MA
影响因子：
4.6
作者：
Chow A;Zhou W;Liu L;Fong MY;Champer J;Van Haute D;Chin AR;Ren X;Gugiu BG;Meng Z;Huang W;Ngo V;Kortylewski M;Wang SE
通讯作者：
Wang SE