Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth.
Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth.
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DOI：
10.1155/2020/5239419
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发表时间：
2020
影响因子：
4.6
通讯作者：
Pervin S
中科院分区：
文献类型：
--
作者：
Jimenez T;Friedman T;Vadgama J;Singh V;Tucker A;Collazo J;Sinha S;Hikim AS;Singh R;Pervin S
乳腺癌是遗传和环境复杂相互作用的结果，改变了免疫和炎症系统，促进了肿瘤的发生。肥胖和吸烟是众所周知的与乳腺癌发展相关的危险因素。已知尼古丁可以减少炎症信号，也可以调节有利于乳腺癌发展的免疫反应。然而，尼古丁和肥胖导致乳腺癌的机制仍然知之甚少。在这项研究中，我们研究了尼古丁（NIC）和高脂饮食（HFD）促进来自非洲裔美国人（AA）三阴性（TN）乳腺癌细胞的HCC 70和HCC 1806异种移植物生长的潜在机制。与单独NIC或HFD相比，喂食HFD并用NIC治疗的免疫缺陷小鼠产生更大的HCC 70和HCC 1806肿瘤。在NIC和HFD存在下异种移植物生长的增加伴随着更高水平的组织驻留巨噬细胞标志物和抗炎细胞因子，包括IL 4、IL 13和IL 10。我们通过体外和离体实验进一步验证了这些参与者的参与。我们发现HFD异种移植物中IL 6和IL 12表达增加的促炎环境。此外，尼古丁或尼古丁加HFD增加了乳腺癌干细胞（MCSC）的亚群和关键脂肪布朗宁标志物CD 137和TMEM 26。有趣的是，在暴露于单独HFD或尼古丁加HFD的异种移植物中，应激诱导的pp 38 MAPK和pERK 1/2上调。划痕试验显示，使用尼古丁乙酰胆碱受体（nAchR）拮抗剂美加明（MEC），尼古丁和棕榈酸酯处理的乳腺癌细胞的增殖/迁移显着减少。此外，异种移植物的发展，免疫缺陷小鼠，喂食HFD加尼古丁，减少共同治疗MEC和SB 203580，pp 38 MAPK抑制剂。我们的研究表明，尼古丁和HFD的存在促进了影响乳腺肿瘤生长的抗炎肿瘤微环境。这项研究还显示了联合治疗在吸烟的肥胖乳腺癌患者中的潜在疗效。
Breast cancer results from a complex interplay of genetics and environment that alters immune and inflammatory systems to promote tumorigenesis. Obesity and cigarette smoking are well-known risk factors associated breast cancer development. Nicotine known to decrease inflammatory signals also modulates immune responses that favor breast cancer development. However, the mechanisms by which nicotine and obesity contribute to breast cancer remain poorly understood. In this study, we examined potential mechanisms by which nicotine (NIC) and high-fat diet (HFD) promote growth of HCC70 and HCC1806 xenografts from African American (AA) triple negative (TN) breast cancer cells. Immunodeficient mice fed on HFD and treated with NIC generated larger HCC70 and HCC1806 tumors when compared to NIC or HFD alone. Increased xenograft growth in the presence of NIC and HFD was accompanied by higher levels of tissue-resident macrophage markers and anti-inflammatory cytokines including IL4, IL13, and IL10. We further validated the involvement of these players by in vitro and ex vivo experiments. We found a proinflammatory milieu with increased expression of IL6 and IL12 in xenografts with HFD. In addition, nicotine or nicotine plus HFD increased a subset of mammary cancer stem cells (MCSCs) and key adipose browning markers CD137 and TMEM26. Interestingly, there was upregulation of stress-induced pp38 MAPK and pERK1/2 in xenografts exposed to HFD alone or nicotine plus HFD. Scratch-wound assay showed marked reduction in proliferation/migration of nicotine and palmitate-treated breast cancer cells with mecamylamine (MEC), a nicotine acetylcholine receptor (nAchR) antagonist. Furthermore, xenograft development in immune-deficient mice, fed HFD plus nicotine, was reduced upon cotreatment with MEC and SB 203580, a pp38MAPK inhibitor. Our study demonstrates the presence of nicotine and HFD in facilitating an anti-inflammatory tumor microenvironment that influences breast tumor growth. This study also shows potential efficacy of combination therapy in obese breast cancer patients who smoke.
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影响因子：
11.2
作者：
Chen L;Mayer JA;Krisko TI;Speers CW;Wang T;Hilsenbeck SG;Brown PH
通讯作者：
Brown PH
影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
DOI：
10.1038/nrendo.2016.32
发表时间：
2016-05
期刊：
Nature reviews. Endocrinology
影响因子：
--
作者：
通讯作者：
--
影响因子：
33.6
作者：
Goel S;Duda DG;Xu L;Munn LL;Boucher Y;Fukumura D;Jain RK
通讯作者：
Jain RK
影响因子：
4.7
作者：
Davidson, Ben;Konstantinovsky, Sophya;Reich, Reuven
通讯作者：
Reich, Reuven