循环肿瘤细胞在上皮和间充质组成上表现出动态变化。
Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition.
机构信息
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
出版信息
Science. 2013 Feb 1;339(6119):580-4. doi: 10.1126/science.1228522.
Abstract
Epithelial-mesenchymal transition (EMT) of adherent epithelial cells to a migratory mesenchymal state has been implicated in tumor metastasis in preclinical models. To investigate its role in human cancer, we characterized EMT in circulating tumor cells (CTCs) from breast cancer patients. Rare primary tumor cells simultaneously expressed mesenchymal and epithelial markers, but mesenchymal cells were highly enriched in CTCs. Serial CTC monitoring in 11 patients suggested an association of mesenchymal CTCs with disease progression. In an index patient, reversible shifts between these cell fates accompanied each cycle of response to therapy and disease progression. Mesenchymal CTCs occurred as both single cells and multicellular clusters, expressing known EMT regulators, including transforming growth factor (TGF)-β pathway components and the FOXC1 transcription factor. These data support a role for EMT in the blood-borne dissemination of human breast cancer.
摘要
上皮-间充质转化（EMT）是指贴壁上皮细胞向迁移的间充质状态的转化，这一过程被认为与临床前模型中的肿瘤转移有关。为了研究其在人类癌症中的作用，我们对来自乳腺癌患者的循环肿瘤细胞（CTC）中的 EMT 进行了特征描述。罕见的原发性肿瘤细胞同时表达间充质和上皮标志物，但间充质细胞在 CTC 中高度富集。对 11 名患者的连续 CTC 监测表明，间充质 CTC 与疾病进展有关。在一名指数患者中，这些细胞命运之间的可逆转变伴随着对治疗和疾病进展的每一次反应循环。间充质 CTC 以单细胞和多细胞簇的形式出现，表达已知的 EMT 调节剂，包括转化生长因子（TGF）-β途径成分和 FOXC1 转录因子。这些数据支持 EMT 在人乳腺癌血源性播散中的作用。
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1
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Nature. 2012 Jul 26;487(7408):510-3. doi: 10.1038/nature11217.
2
To differentiate or not--routes towards metastasis.是分化还是不分化——通往转移的途径。
Nat Rev Cancer. 2012 May 11;12(6):425-36. doi: 10.1038/nrc3265.
3
Viable circulating tumour cell detection using multiplex RNA in situ hybridisation predicts progression-free survival in metastatic breast cancer patients.采用多重 RNA 原位杂交技术检测有活力的循环肿瘤细胞可预测转移性乳腺癌患者的无进展生存期。
Br J Cancer. 2012 May 22;106(11):1790-7. doi: 10.1038/bjc.2012.137. Epub 2012 Apr 26.
4
Anoikis resistance: an essential prerequisite for tumor metastasis.失巢凋亡抗性：肿瘤转移的必要前提条件。
Int J Cell Biol. 2012;2012:306879. doi: 10.1155/2012/306879. Epub 2012 Feb 23.
5
Epithelial-mesenchymal transition in breast cancer correlates with high histological grade and triple-negative phenotype.乳腺癌中的上皮-间充质转化与高组织学分级和三阴性表型相关。
Histopathology. 2012 May;60(6B):E87-95. doi: 10.1111/j.1365-2559.2012.04195.x. Epub 2012 Mar 22.
6
Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors.描述上皮性肿瘤患者循环肿瘤细胞聚集体的特征。
Phys Biol. 2012 Feb;9(1):016001. doi: 10.1088/1478-3975/9/1/016001. Epub 2012 Feb 3.
7
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Cell. 2012 Jan 20;148(1-2):349-61. doi: 10.1016/j.cell.2011.11.025.
8
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9
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10
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