Adipocytes induce distinct gene expression profiles in mammary tumor cells and enhance inflammatory signaling in invasive breast cancer cells.
Adipocytes induce distinct gene expression profiles in mammary tumor cells and enhance inflammatory signaling in invasive breast cancer cells.
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DOI：
10.1038/s41598-018-27210-w
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发表时间：
2018-06-21
影响因子：
4.6
通讯作者：
Stadler SC
中科院分区：
文献类型：
--
作者：
Nickel A;Blücher C;Kadri OA;Schwagarus N;Müller S;Schaab M;Thiery J;Burkhardt R;Stadler SC
肥胖是乳腺癌的一个已知危险因素。由于肥胖率在全球范围内不断上升，了解脂肪组织和乳腺肿瘤之间相互作用的分子细节成为一项紧迫的任务。为了研究共存脂肪细胞诱导的乳腺癌细胞的潜在分子变化，我们使用了不同乳腺癌细胞系（MCF-7和T47 D：ER+/PR+/HER 2 −和MDA-MB-231：ER−/PR−/HER 2 −）和小鼠3 T3-L1脂肪细胞的共培养系统。在这里，我们报告，与脂肪细胞共培养揭示了不同乳腺癌细胞系的全球基因表达模式的不同变化。我们的微阵列数据显示，在两种ER+细胞系中，顶部上调的基因显示激素受体靶基因的显著富集。在三阴性MDA-MB-231细胞中，与脂肪细胞共培养导致促炎基因的诱导，主要涉及NF-κB信号通路的基因。此外，共培养的MDA-MB-231细胞显示促炎性白细胞介素IL-6和IL-8的分泌增加。使用特定的NF-κB抑制剂，这些作用显著降低。最后，在与脂肪细胞共培养后，三阴性乳腺癌细胞的迁移能力显著增加，表明增强的侵袭性细胞表型。总之，我们的研究表明，脂肪细胞分泌的因子对乳腺癌细胞的分子生物学有重大影响。
Obesity is a known risk factor for breast cancer. Since obesity rates are constantly rising worldwide, understanding the molecular details of the interaction between adipose tissue and breast tumors becomes an urgent task. To investigate potential molecular changes in breast cancer cells induced by co-existing adipocytes, we used a co-culture system of different breast cancer cell lines (MCF-7 and T47D: ER+/PR+/HER2− and MDA-MB-231: ER−/PR−/HER2−) and murine 3T3-L1 adipocytes. Here, we report that co-culture with adipocytes revealed distinct changes in global gene expression pattern in the different breast cancer cell lines. Our microarray data revealed that in both ER+ cell lines, top upregulated genes showed significant enrichment for hormone receptor target genes. In triple-negative MDA-MB-231 cells, co-culture with adipocytes led to the induction of pro-inflammatory genes, mainly involving genes of the Nf-κB signaling pathway. Moreover, co-cultured MDA-MB-231 cells showed increased secretion of the pro-inflammatory interleukins IL-6 and IL-8. Using a specific NF-κB inhibitor, these effects were significantly decreased. Finally, migratory capacities were significantly increased in triple-negative breast cancer cells upon co-culture with adipocytes, indicating an enhanced aggressive cell phenotype. Together, our studies illustrate that factors secreted by adipocytes have a significant impact on the molecular biology of breast cancer cells.
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影响因子：
11.2
作者：
Hartman ZC;Poage GM;den Hollander P;Tsimelzon A;Hill J;Panupinthu N;Zhang Y;Mazumdar A;Hilsenbeck SG;Mills GB;Brown PH
通讯作者：
Brown PH
影响因子：
6.1
作者：
Keator, Christopher S.;Mah, Kuni;Slayden, Ov D.
通讯作者：
Slayden, Ov D.
影响因子：
4.4
作者：
Kallio MA;Tuimala JT;Hupponen T;Klemelä P;Gentile M;Scheinin I;Koski M;Käki J;Korpelainen EI
通讯作者：
Korpelainen EI
DOI：
10.1016/j.bbrc.2011.06.101
发表时间：
2011-07-22
影响因子：
3.1
作者：
Bochet, Ludivine;Meulle, Aline;Muller, Catherine
通讯作者：
Muller, Catherine
影响因子：
45.3
作者：
Ewertz, Marianne;Jensen, Maj-Britt;Cold, Soren
通讯作者：
Cold, Soren