Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis.

Mesenchymal and stemness circulating tumor cells in early breast cancer diagnosis.
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DOI:
10.1186/1471-2407-12-114
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发表时间:
2012-03-23
期刊:
影响因子:
3.8
通讯作者:
Rigaud M
Rigaud M
中科院分区:
医学2区
文献类型:
--
作者:
Barrière G;Riouallon A;Renaudie J;Tartary M;Rigaud M

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上皮间质转化(EMT)是可能参与上皮癌细胞扩散的关键事件。这一过程使它们能够获得迁移/侵袭特性,从而促进肿瘤和转移扩散。为了了解这一事件是否是乳腺癌的早期事件,我们开展了一项临床试验。该方案的目的是在初步诊断时检测具有间充质和/或干性特征的循环肿瘤细胞。招募了无内脏或骨转移的乳腺癌患者 (n = 61),并对这些去分化循环肿瘤细胞 (ddCTC) 进行了分析。 AdnaGen方法用于富集细胞选择。然后,通过 RT-PCR 研究以下基因来表征 ddCTC:PI3Kα、Akt-2、Twist1(EMT 标记)以及 ALDH1、Bmi1 和 CD44(干性指标)。在研究的原发性乳腺癌队列中,39% 的病例检测到 ddCTC 的存在。除了淋巴结状态之外,这种阳性结果与肿瘤临床病理因素无关。我们的数据独特地证明,体内 EMT 发生在原发性肿瘤中,并且与癌症疾病早期肿瘤细胞内渗能力的增强相关。这些结果表明,针对显示间充质或干性特征的细胞的循环肿瘤细胞的分析可能有助于在临床试验中评估新药。
Epithelial mesenchymal transition (EMT) is a crucial event likely involved in dissemination of epithelial cancer cells. This process enables them to acquire migratory/invasive properties, contributing to tumor and metastatic spread. To know if this event is an early one in breast cancer, we developed a clinical trial. The aim of this protocol was to detect circulating tumor cells endowed with mesenchymal and/or stemness characteristics, at the time of initial diagnosis. Breast cancer patients (n = 61), without visceral or bone metastasis were enrolled and analysis of these dedifferentiated circulating tumor cells (ddCTC) was realized. AdnaGen method was used for enrichment cell selection. Then, ddCTC were characterized by RT-PCR study of the following genes: PI3Kα, Akt-2, Twist1 (EMT markers) and ALDH1, Bmi1 and CD44 (stemness indicators). Among the studied primary breast cancer cohort, presence of ddCTC was detected in 39% of cases. This positivity is independant from tumor clinicopathological factors apart from the lymph node status. Our data uniquely demonstrated that in vivo EMT occurs in the primary tumors and is associated with an enhanced ability of tumor cells to intravasate in the early phase of cancer disease. These results suggest that analysis of circulating tumor cells focused on cells showing mesenchymal or stemness characteristics might facilitate assessment of new drugs in clinical trials.
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