Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue.
Paracrine Interactions between Adipocytes and Tumor Cells Recruit and Modify Macrophages to the Mammary Tumor Microenvironment: The Role of Obesity and Inflammation in Breast Adipose Tissue.
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DOI：
10.3390/cancers7010143
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发表时间：
2015-01-15
期刊：
影响因子：
5.2
通讯作者：
Torroella-Kouri M
中科院分区：
文献类型：
--
作者：
Santander AM;Lopez-Ocejo O;Casas O;Agostini T;Sanchez L;Lamas-Basulto E;Carrio R;Cleary MP;Gonzalez-Perez RR;Torroella-Kouri M
肥胖与乳腺癌之间的关系一直集中在血清因素上。然而，乳腺含有脂肪组织(AT)，这可能使脂肪细胞和肿瘤细胞之间的串扰有助于肿瘤巨噬细胞的募集。我们假设肥胖女性的乳房AT(BAT)是发炎的，并且在乳腺癌的发生中起主要作用。采用小鼠巨噬细胞、乳腺肿瘤细胞和脂肪细胞共培养的方法，研究了这种相互作用对巨噬细胞趋化作用的影响。巨噬细胞暴露于脂肪细胞和肿瘤旁分泌因子瘦素、CCL2和月桂酸(单独或联合作用)。在细胞上清液中，Luminex发现了更多具有趋化和其他促肿瘤功能的分子。重点关注脂肪因子瘦素，它已被证明在乳腺癌发病机制中发挥核心作用，表明它调节巨噬细胞的表型和功能。体内实验表明，肥胖小鼠的乳腺肿瘤更大，肥胖肿瘤携带者的BAT含有更多的巨噬细胞/CLS和肥大的脂肪细胞，从而证实了它更容易发炎。此外，肥胖小鼠的肿瘤远端比瘦小鼠更容易发炎。我们的结果显示，BAT在肥胖的乳腺癌发生中发挥了作用。
The relationship between obesity and breast cancer (BC) has focused on serum factors. However, the mammary gland contains adipose tissue (AT) which may enable the crosstalk between adipocytes and tumor cells contributing to tumor macrophage recruitment. We hypothesize that the breast AT (bAT) is inflamed in obese females and plays a major role in breast cancer development. The effects of this interplay on macrophage chemotaxis were examined in vitro, using co-cultures of mouse macrophages, mammary tumor cells and adipocytes. Macrophages were exposed to the adipocyte and tumor paracrine factors leptin, CCL2 and lauric acid (alone or in combinations). In cell supernatants Luminex identified additional molecules with chemotactic and other pro-tumor functions. Focus on the adipokine leptin, which has been shown to have a central role in breast cancer pathogenesis, indicated it modulates macrophage phenotypes and functions. In vivo experiments demonstrate that mammary tumors from obese mice are larger and that bAT from obese tumor-bearers contains higher numbers of macrophages/CLS and hypertrophic adipocytes than bAT from lean tumor-bearers, thus confirming it is more inflamed. Also, bAT distal from the tumor is more inflamed in obese than in lean mice. Our results reveal that bAT plays a role in breast cancer development in obesity.
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瘦素信号传导抑制可在雌激素受体阳性或阴性乳腺癌中产生有效的抗肿瘤活性。
影响因子：
7.4
作者：
Gonzalez, Ruben Rene;Watters, Amber;Xu, Yanbo;Singh, Udai P.;Mann, David R.;Rueda, Bo R.;Penichet, Manuel L.
通讯作者：
Penichet, Manuel L.
影响因子：
5.5
作者：
Gruen, Marnie L.;Hao, Mingming;Hasty, Alyssa H.
通讯作者：
Hasty, Alyssa H.
影响因子：
5.2
作者：
Caso, Raul;Silvera, Risset;Torroella-Kouri, Marta
通讯作者：
Torroella-Kouri, Marta
影响因子：
4.9
作者：
Cleary, MP;Grande, JP;Maihle, NJ
通讯作者：
Maihle, NJ
影响因子：
7.4
作者：
Dogan, Soner;Hu, Xin;Cleary, Margot P.
通讯作者：
Cleary, Margot P.