Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy.
Expression of epithelial-mesenchymal transition-inducing transcription factors in primary breast cancer: The effect of neoadjuvant therapy.
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DOI：
10.1002/ijc.26037
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发表时间：
2012-02-15
影响因子：
6.4
通讯作者：
Reuben, James M.
中科院分区：
文献类型：
--
作者：
Mego, Michal;Mani, Sendurai A.;Lee, Bang-Ning;Li, Changping;Evans, Kurt W.;Cohen, Evan N.;Gao, Hui;Jackson, Summer A.;Giordano, Antonio;Hortobagyi, Gabriel N.;Cristofanilli, Massimo;Lucci, Anthony;Reuben, James M.
关键词：
上皮性癌细胞在进入外周循环之前可能经历上皮间充质转化(EMT)。在接受EMT时，循环中的肿瘤细胞(CTCs)会丢失上皮标记物，并可能逃脱常规方法的检测。因此，我们进行了一项初步研究，以研究原发性乳腺癌(PBC)患者外周血中肿瘤细胞中EMT诱导转录因子(TF)的mRNA转录。从52例I-III期PBC患者和30例健康献血者(HD)外周血中分离单个核细胞，并依次去除EPCAM+细胞和CD45+白细胞，以下简称CD45CD45−。用定量逆转录聚合酶链式反应(qRT-PCR法)检测EMT诱导的−细胞中Twist1、SNAIL1、SLUG、ZEB1和FOXC2的表达水平。HD的CD45EMF细胞片段的最高表达水平被用来确定来自PBC患者的样本是否过表达任何EMT诱导的−。总体而言，15.4%的PBC患者过度表达至少一种EMT诱导的Tf转录本。接受新辅助治疗(NAT)的PBC患者比未接受NAT治疗的患者更有可能检测到任何EMT诱导的TF转录本的过度表达(P=0.003)。同时，在38例患者中有7例(18.4%)CellSearch®和42例患者中有15例(35.7%)通过™检测到CTCs。通过CellSearch®或Adna测试™测量的CTC的存在之间没有关联。综上所述，我们的结果表明，PBC患者外周循环中可能存在具有EMT表型的CTC，而NAT不能消除接受EMT的CTC。
Epithelial cancer cells are likely to undergo epithelial mesenchymal transition (EMT) prior to entering the peripheral circulation. By undergoing EMT, circulating tumor cells (CTCs) lose epithelial markers and may escape detection by conventional methods. Therefore, we conducted a pilot study to investigate mRNA transcripts of EMT-inducing transcription factors (TFs) in tumor cells from the peripheral blood (PB) of primary breast cancer (PBC) patients. Peripheral blood mononuclear cells were isolated from 52 stages I–III PBC patients and 30 healthy donors (HD) and sequentially depleted of EpCAM+ cells and CD45+ leukocytes, henceforth referred to as CD45−. The expression levels of EMT-inducing TFs (TWIST1, SNAIL1, SLUG, ZEB1, and FOXC2) in the CD45− cells were determined using qRT-PCR. The highest level of expression by the CD45− cell fraction of HD was used as “cut off” to determine if samples from PBC patients overexpressed any EMT-inducing TFs. In total, 15.4% of PBC patients overexpressed at least one of the EMT-inducing TF transcripts. Overexpression of any EMT-inducing TF transcripts was more likely to be detected in PBC patients who received neoadjuvant therapies (NAT) than patients who received no NAT (P = 0.003). Concurrently, CTCs were detected in 7 out of 38 (18.4%) patients by CellSearch® and 15 out of 42 (35.7%) patients by AdnaTest™. There was no association between the presence of CTCs measured by CellSearch® or AdnaTest™. In summary, our results demonstrate that CTCs with EMT phenotype may occur in the peripheral circulation of PBC patients and NAT is unable to eliminate CTCs undergoing EMT.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
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影响因子：
11.5
作者：
Li, Qing-Quan;Xu, Jing-Da;Xu, Zu-De
通讯作者：
Xu, Zu-De
影响因子：
64.5
作者：
Yang, J;Mani, SA;Weinberg, RA
通讯作者：
Weinberg, RA
影响因子：
11.5
作者：
Ignatiadis, Michail;Kallergi, Galatea;Mavroudis, Dimitris
通讯作者：
Mavroudis, Dimitris
DOI：
10.1073/pnas.0606599104
发表时间：
2007-01-09
影响因子：
11.1
作者：
Woodward, Wendy A.;Chen, Mercy S.;Rosen, Jeffrey M.
通讯作者：
Rosen, Jeffrey M.