CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms.
CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms.
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DOI：
10.1007/s10911-018-9407-1
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发表时间：
2018-12
影响因子：
2.5
通讯作者：
Cheng N
中科院分区：
文献类型：
--
作者：
Bernard S;Myers M;Fang WB;Zinda B;Smart C;Lambert D;Zou A;Fan F;Cheng N
随着筛查方法的改进，女性中诊断出的异常乳腺病变数量随着时间的推移而增加。然而，目前尚不清楚这些乳腺病变是否会发展为浸润性癌症。为了更有效地预测乳腺病变的结果并确定更合适的治疗方案，重要的是要了解调节非侵入性病变进展为侵入性乳腺癌的潜在机制。浸润性乳腺癌的一个标志是成纤维细胞的积累。乳腺中的成纤维细胞增殖和活化部分受转化生长因子β 1途径（TGF-β）调节。在动物模型中，TGF-β对CCL 2和CXCL 1趋化因子表达的抑制与乳腺癌的转移进展相关。在这里，我们表明，在C57 BL/6小鼠的小鼠乳腺中的多瘤病毒中T病毒抗原的转基因过表达导致缓慢生长的非侵入性病变，以阶段依赖的方式进展为浸润性癌。浸润性癌与成纤维细胞的积累相关，其显示TGF-β表达降低和高水平的CXCL 1，但不是CCL 2。使用共移植模型，我们表明成纤维细胞中TGF-β信号转导的减少通过增强CXCL 1/CXCR 2依赖性机制促进乳腺癌进展。利用细胞培养模型，我们发现CXCL 1通过NF-κB、AKT、Stat 3和p42/44 MAPK依赖的机制介导乳腺癌细胞的侵袭。这些研究为浸润前病变的进展提供了新的机制见解，并确定了新的基质生物标志物，具有重要的预后意义。
With improved screening methods, the numbers of abnormal breast lesions diagnosed in women have been increasing over time. However, it remains unclear whether these breast lesions will develop into invasive cancers. To more effectively predict the outcome of breast lesions and determine a more appropriate course of treatment, it is important to understand the underlying mechanisms that regulate progression of non-invasive lesions to invasive breast cancers. A hallmark of invasive breast cancers is the accumulation of fibroblasts. Fibroblast proliferation and activation in the mammary gland is in part regulated by the Transforming Growth Factor beta1 pathway (TGF-β). In animal models, TGF-β suppression of CCL2 and CXCL1 chemokine expression is associated with metastatic progression of mammary carcinomas. Here, we show that transgenic overexpression of the Polyoma middle T viral antigen in the mouse mammary gland of C57BL/6 mice results in slow growing non-invasive lesions that progress to invasive carcinomas in a stage dependent manner. Invasive carcinomas are associated with accumulation of fibroblasts that show decreased TGF-β expression and high levels of CXCL1, but not CCL2. Using co-transplant models, we show that decreased TGF-β signaling in fibroblasts contribute to mammary carcinoma progression through enhancement of CXCL1/CXCR2 dependent mechanisms. Using cell culture models, we show that CXCL1 mediated mammary carcinoma cell invasion through NF-κB, AKT, Stat3 and p42/44MAPK dependent mechanisms. These studies provide novel mechanistic insight into the progression of pre-invasive lesions and identify new stromal biomarkers, with important prognostic implications.
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影响因子：
4.8
作者：
Chang, Qing;Bournazou, Eirini;Bromberg, Jacqueline
通讯作者：
Bromberg, Jacqueline
DOI：
10.1186/s13058-016-0740-2
发表时间：
2016-08-11
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Bussard KM;Mutkus L;Stumpf K;Gomez-Manzano C;Marini FC
通讯作者：
Marini FC
影响因子：
64.5
作者：
Acharyya S;Oskarsson T;Vanharanta S;Malladi S;Kim J;Morris PG;Manova-Todorova K;Leversha M;Hogg N;Seshan VE;Norton L;Brogi E;Massagué J
通讯作者：
Massagué J
影响因子：
4.8
作者：
Dhawan, P;Richmond, A
通讯作者：
Richmond, A
影响因子：
11.2
作者：
Cheng, Nikki;Chytil, Anna;Mosesi, Harold L.
通讯作者：
Mosesi, Harold L.