Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition.
Inflammatory mediators in breast cancer: coordinated expression of TNFα & IL-1β with CCL2 & CCL5 and effects on epithelial-to-mesenchymal transition.
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DOI：
10.1186/1471-2407-11-130
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发表时间：
2011-04-12
期刊：
影响因子：
3.8
通讯作者：
Ben-Baruch A
中科院分区：
文献类型：
--
作者：
Soria G;Ofri-Shahak M;Haas I;Yaal-Hahoshen N;Leider-Trejo L;Leibovich-Rivkin T;Weitzenfeld P;Meshel T;Shabtai E;Gutman M;Ben-Baruch A
炎性趋化因子CCL 2（MCP-1）和CCL 5（RANTES）以及炎性细胞因子TNFα和IL-1β被证明有助于乳腺癌的发展和转移。在这项研究中，我们希望确定这些因素之间是否有关联，沿着乳腺癌进展的沿着阶段，并确定这些因素对疾病进程的可能影响。通过免疫组化测定诊断为以下疾病的患者中CCL 2、CCL 5、TNFα和IL-1β的表达：（1）良性乳腺疾病（=健康个体）;（2）导管原位癌（DCIS）;（3）浸润性导管癌无复发（IDC-无复发）;（4）IDC-复发。根据所得结果，乳腺肿瘤细胞受到炎性细胞因子的刺激，并通过流式细胞术、共聚焦分析以及粘附、迁移和侵袭实验来确定上皮向间充质转化（EMT）。CCL 2、CCL 5、TNFα和IL-1β在正常乳腺上皮细胞中的表达率极低，而在3组乳腺癌患者的肿瘤细胞中的表达率显著升高。在DCIS和IDC无复发患者中，发现肿瘤细胞中的CCL 2和CCL 5与TNFα和IL-1β显著相关。在IDC复发组中，CCL 2和CCL 5的表达伴随着TNFα和IL-1β表达的进一步升高。这些结果表明TNFα和IL-1β在乳腺癌中的进展相关作用，如以下事实所示：（1）与DCIS或IDC无复发组相比，IDC复发组的肿瘤具有显著更高的TNFα和IL-1β持久性;（2）TNFα持续刺激肿瘤细胞，（3）结合相关临床指标分析，提示IL-1β与其他促癌因子共同作用，促进疾病复发。提示CCL 2和CCL 5、TNFα和IL-1β的协同表达可能对疾病的发展起重要作用，TNFα和IL-1β可能促进疾病的复发。需要进一步的体外和体内研究来确定四个因素在乳腺癌中的联合功效，以及分析它们在乳腺癌中的联合靶向。
The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFα & IL-1β were shown to contribute to breast cancer development and metastasis. In this study, we wished to determine whether there are associations between these factors along stages of breast cancer progression, and to identify the possible implications of these factors to disease course. The expression of CCL2, CCL5, TNFα and IL-1β was determined by immunohistochemistry in patients diagnosed with: (1) Benign breast disorders (=healthy individuals); (2) Ductal Carcinoma In Situ (DCIS); (3) Invasive Ducal Carcinoma without relapse (IDC-no-relapse); (4) IDC-with-relapse. Based on the results obtained, breast tumor cells were stimulated by the inflammatory cytokines, and epithelial-to-mesenchymal transition (EMT) was determined by flow cytometry, confocal analyses and adhesion, migration and invasion experiments. CCL2, CCL5, TNFα and IL-1β were expressed at very low incidence in normal breast epithelial cells, but their incidence was significantly elevated in tumor cells of the three groups of cancer patients. Significant associations were found between CCL2 & CCL5 and TNFα & IL-1β in the tumor cells in DCIS and IDC-no-relapse patients. In the IDC-with-relapse group, the expression of CCL2 & CCL5 was accompanied by further elevated incidence of TNFα & IL-1β expression. These results suggest progression-related roles for TNFα and IL-1β in breast cancer, as indeed indicated by the following: (1) Tumors of the IDC-with-relapse group had significantly higher persistence of TNFα and IL-1β compared to tumors of DCIS or IDC-no-relapse; (2) Continuous stimulation of the tumor cells by TNFα (and to some extent IL-1β) has led to EMT in the tumor cells; (3) Combined analyses with relevant clinical parameters suggested that IL-1β acts jointly with other pro-malignancy factors to promote disease relapse. Our findings suggest that the coordinated expression of CCL2 & CCL5 and TNFα & IL-1β may be important for disease course, and that TNFα & IL-1β may promote disease relapse. Further in vitro and in vivo studies are needed for determination of the joint powers of the four factors in breast cancer, as well as analyses of their combined targeting in breast cancer.
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影响因子：
6
作者：
Ali, S;Kaur, J;Patel, KD
通讯作者：
Patel, KD
影响因子：
3.8
作者：
Bozcuk, H;Uslu, G;Savas, B
通讯作者：
Savas, B
影响因子：
3.1
作者：
Bertazza, Loris;Mocellin, Simone
通讯作者：
Mocellin, Simone
影响因子：
6
作者：
De Larco, JE;Wuertz, BRK;Furcht, LT
通讯作者：
Furcht, LT
DOI：
10.1186/bcr1648
发表时间：
2007
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Chavey C;Bibeau F;Gourgou-Bourgade S;Burlinchon S;Boissière F;Laune D;Roques S;Lazennec G
通讯作者：
Lazennec G