Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis.
Circulating tumor cell clusters are oligoclonal precursors of breast cancer metastasis.
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DOI：
10.1016/j.cell.2014.07.013
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发表时间：
2014-08-28
期刊：
影响因子：
64.5
通讯作者：
Maheswaran S
中科院分区：
文献类型：
--
作者：
Aceto N;Bardia A;Miyamoto DT;Donaldson MC;Wittner BS;Spencer JA;Yu M;Pely A;Engstrom A;Zhu H;Brannigan BW;Kapur R;Stott SL;Shioda T;Ramaswamy S;Ting DT;Lin CP;Toner M;Haber DA;Maheswaran S
循环肿瘤细胞簇（ctc -簇）存在于癌症患者的血液中，但它们对转移的贡献尚未明确。使用带有标记乳腺肿瘤的小鼠模型，我们证明ctc簇起源于寡克隆肿瘤细胞群，而不是来自血管内聚集事件。尽管与单个ctc相比，ctc簇在循环中很少见，但其转移潜力增加了23-50倍。在乳腺癌患者中，ctc簇和单个ctc的单细胞分辨率RNA测序，在个体血液样本中匹配，确定细胞连接成分血小板红蛋白高度差异表达。在小鼠模型中，敲低血小板红蛋白可消除ctc簇的形成并抑制肺转移。在乳腺癌患者中，ctc簇的丰度和肿瘤血小板红蛋白的高水平都表明不良后果。因此，ctc簇源于原发肿瘤细胞的多细胞分组，通过血小板蛋白依赖的细胞间粘附结合在一起，虽然罕见，但它们极大地促进了癌症的转移扩散。
Clusters of circulating tumor cells (CTC-clusters) are present in the blood of patients with cancer but their contribution to metastasis is not well defined. Using mouse models with tagged mammary tumors, we demonstrate that CTC-clusters arise from oligoclonal tumor cell groupings and not from intravascular aggregation events. Although rare in the circulation compared with single CTCs, CTC-clusters have 23-50-fold increased metastatic potential. In patients with breast cancer, single-cell resolution RNA sequencing of CTC-clusters and single CTCs, matched within individual blood samples, identifies the cell junction component plakoglobin as highly differentially expressed. In mouse models, knockdown of plakoglobin abrogates CTC-cluster formation and suppresses lung metastases. In breast cancer patients, both abundance of CTC-clusters and high tumor plakoglobin levels denote adverse outcomes. Thus, CTC-clusters are derived from multicellular groupings of primary tumor cells held together through plakoglobin-dependent intercellular adhesion, and while rare, they greatly contribute to the metastatic spread of cancer.
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影响因子：
28.2
作者：
Miyamoto DT;Lee RJ;Stott SL;Ting DT;Wittner BS;Ulman M;Smas ME;Lord JB;Brannigan BW;Trautwein J;Bander NH;Wu CL;Sequist LV;Smith MR;Ramaswamy S;Toner M;Maheswaran S;Haber DA
通讯作者：
Haber DA
影响因子：
8.4
作者：
FIDLER, IJ
通讯作者：
FIDLER, IJ
影响因子：
2.5
作者：
Alford, Deborah;Taylor-Papadimitriou, Joyce
通讯作者：
Taylor-Papadimitriou, Joyce
影响因子：
2.9
作者：
Robson, Ewan J. D.;Khaled, Walid T.;Watson, Christine J.
通讯作者：
Watson, Christine J.
影响因子：
4.8
作者：
Hakimelahi, S;Parker, HR;Pasdar, M
通讯作者：
Pasdar, M