Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.
Reciprocal interactions between breast tumor and its adipose microenvironment based on a 3D adipose equivalent model.
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DOI：
10.1371/journal.pone.0066284
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Caldefie-Chézet F
中科院分区：
文献类型：
--
作者：
Delort L;Lequeux C;Dubois V;Dubouloz A;Billard H;Mojallal A;Damour O;Vasson MP;Caldefie-Chézet F
乳腺癌已成为工业化国家妇女中最常见的癌症。肥胖已被公认为一种危险因素，特别是由于随之而来的脂肪因子的分泌；越来越多的证据表明，存在于乳腺肿瘤微环境中的细胞和因子，如成纤维细胞、前脂肪细胞、脂肪细胞及其分泌物，在肿瘤微环境中发挥着重要作用。为了研究微环境如何影响乳腺癌的生长，我们开发了一种新的三维脂肪模型，该模型是用正常的人角质形成细胞或乳腺癌细胞系上皮化的。这些模拟了乳房肿瘤与脂肪微环境的接触，并允许监测细胞之间的相互作用。瘦素和脂联素是两种主要的脂肪因子，它们各自的受体ObRt和AdipoR1在模型中表达，但第二种脂联素受体AdipoR2不表达。前脂肪细胞与乳腺癌细胞系接触时，向脂肪细胞的分化更大。乳腺癌细胞系与微环境的接触通过增加参与细胞增殖（cyclinD1， MAPK）、血管生成（MMP9， VEGF）和激素通路（ESR1, IL6）的基因表达，完全改变了它们的转录程序。这种三维脂肪模型为乳腺癌细胞与其脂肪微环境之间的相互作用提供了新的见解，并为开发治疗癌症和肥胖的新药提供了工具。
Breast cancer has become the most common cancer among women in industrialized countries. Obesity is well established as a risk factor, in particular owing to the attendant secretion of the entities called adipokines; there is growing evidence for a role of cells and factors present in the mammary tumor microenvironment such as fibroblasts, preadipocytes, adipocytes and their secretions. To study how the microenvironment influences breast cancer growth, we developed a novel tridimensional adipose model epithelialized with normal human keratinocytes or with breast cancer cell lines. These mimicked a breast tumor in contact with an adipose microenvironment and allowed monitoring of the interactions between the cells. Leptin and adiponectin, two major adipokines, and their respective receptors, ObRt and AdipoR1, were expressed in the model, but not the second adiponectin receptor, AdipoR2. The differentiation of preadipocytes into adipocytes was greater when they were in contact with the breast cancer cell lines. The contact of breast cancer cell lines with the microenvironment completely modified their transcriptional programs by increasing the expression of genes involved in cell proliferation (cyclinD1, MAPK), angiogenesis (MMP9, VEGF) and hormonal pathways (ESR1, IL6). This tridimensional adipose model provides new insights into the interactions between breast cancer cells and their adipose microenvironment, and provides a tool to develop new drugs for the treatment of both cancer and obesity.
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影响因子：
4.7
作者：
Maccio, Antonio;Madeddu, Clelia;Mantovani, Giovanni
通讯作者：
Mantovani, Giovanni
影响因子：
2.4
作者：
La Vecchia, C
通讯作者：
La Vecchia, C
影响因子：
4.1
作者：
Mawson, A;Lai, A;Sarcevic, B
通讯作者：
Sarcevic, B
影响因子：
6.4
作者：
Binai, Nadine A.;Damert, Annette;Wessler, Silja
通讯作者：
Wessler, Silja
影响因子：
9.8
作者：
BJORNTORP, P;KARLSSON, M;PETTERSSON, P
通讯作者：
PETTERSSON, P