Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling.
Macrophages Enhance Migration in Inflammatory Breast Cancer Cells via RhoC GTPase Signaling.
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DOI：
10.1038/srep39190
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发表时间：
2016-12-19
影响因子：
4.6
通讯作者：
Merajver SD
中科院分区：
文献类型：
--
作者：
Allen SG;Chen YC;Madden JM;Fournier CL;Altemus MA;Hiziroglu AB;Cheng YH;Wu ZF;Bao L;Yates JA;Yoon E;Merajver SD
炎症性乳腺癌（IBC）是乳腺癌中最致命的形式。所有的IBC患者都有淋巴结受累，三分之一的患者在诊断时已经有远处转移。这种转移倾向是IBC的标志，将其与低致死性非炎性乳腺癌（nIBC）区分开来。已经进行了遗传分析研究以区分IBC和nIBC，但尚未鉴定出IBC癌细胞特异性基因特征。我们假设，一个肿瘤的外在因素，特别是肿瘤相关的巨噬细胞，促进和有助于IBC的极端转移表型。为此，我们研究了巨噬细胞条件培养基（MCM）对IBC的影响。我们发现，两个IBC细胞系是超反应MCM相比，正常样乳腺癌和侵略性nIBC细胞系。我们进一步询问了IBC的高反应性MCM使用微流体迁移装置，它允许单个细胞迁移路径跟踪。我们发现MCM“启动”IBC细胞的细胞机制，使其响应于化学引诱物而变得极度迁移。我们确定MCM中的白细胞介素-6，-8和-10足以刺激这种增强的IBC迁移效应，并且已知的转移癌基因RhoC GTdR是增强迁移反应所必需的。
Inflammatory breast cancer (IBC) is the most lethal form of breast cancer. All IBC patients have lymph node involvement and one-third of patients already have distant metastasis at diagnosis. This propensity for metastasis is a hallmark of IBC distinguishing it from less lethal non-inflammatory breast cancers (nIBC). Genetic profiling studies have been conducted to differentiate IBC from nIBC, but no IBC cancer-cell-specific gene signature has been identified. We hypothesized that a tumor-extrinsic factor, notably tumor-associated macrophages, promotes and contributes to IBC’s extreme metastatic phenotype. To this end, we studied the effect of macrophage-conditioned media (MCM) on IBC. We show that two IBC cell lines are hyper-responsive to MCM as compared to normal-like breast and aggressive nIBC cell lines. We further interrogated IBC’s hyper-responsiveness to MCM using a microfluidic migration device, which permits individual cell migration path tracing. We found the MCM “primes” the IBC cells’ cellular machinery to become extremely migratory in response to a chemoattractant. We determined that interleukins −6, −8, and −10 within the MCM are sufficient to stimulate this enhanced IBC migration effect, and that the known metastatic oncogene, RhoC GTPase, is necessary for the enhanced migration response.
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影响因子：
6.2
作者：
Bertucci, Francois;Finetti, Pascal;Viens, Patrice
通讯作者：
Viens, Patrice
影响因子：
50.5
作者：
Masuda, H.;Brewer, T. M.;Ueno, N. T.
通讯作者：
Ueno, N. T.
影响因子：
5.7
作者：
Burgos-Ojeda D;Wu R;McLean K;Chen YC;Talpaz M;Yoon E;Cho KR;Buckanovich RJ
通讯作者：
Buckanovich RJ
影响因子：
4
作者：
Joglekar, Madhura;Elbazanti, Weam O.;van Golen, Kenneth L.
通讯作者：
van Golen, Kenneth L.
影响因子：
10.3
作者：
Hance, KW;Anderson, WF;Levine, PH
通讯作者：
Levine, PH