EMT status of circulating breast cancer cells and impact of fluidic shear stress
EMT status of circulating breast cancer cells and impact of fluidic shear stress
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循环乳腺癌细胞的 EMT 状态和流体剪切应力的影响
DOI：
10.1016/j.yexcr.2022.113385
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发表时间：
2022-12-01
影响因子：
3.7
通讯作者：
Li, Min
中科院分区：
文献类型：
--
作者：
Jin, Yanling;Cai, Wei;Li, Min
循环肿瘤细胞（CTC）在乳腺癌的转移和复发中起着至关重要的作用。CTC在上皮-间质转化（EMT）阶段是高度异质性的，但在不同EMT阶段的表型和生物学特征仍然不清楚。我们进行了乳腺癌的原位小鼠（4 T1）模型以分离CTC并鉴定了CTC的两种表型：中间E/M和间充质CTC。MTT法、集落形成实验、Transwell迁移实验和侵袭实验检测细胞增殖、集落形成、迁移和侵袭能力。与原发性肿瘤细胞相比，中间E/M和间充质CTC都表现出较低的增殖、集落形成和侵袭速率。间充质CTCs具有较高的侵袭率，但较低的增殖和集落形成率比中间E/M CTCs。它们在体内也表现出比原代肿瘤细胞更低的生长和转移率，但间充质CTC比中间E/M CTC具有更高的转移率。流体剪切应力诱导了CTC的EMT转变。通过对CTC蛋白质组学的综合分析，发现了在两类CTC及其原代肿瘤细胞中差异表达的蛋白质。
Circulating tumor cells (CTCs) play a vital role in the metastasis and recurrence of breast cancer. CTCs are highly heterogeneous at the stage of Epithelial-to-Mesenchymal Transition (EMT), but the phenotypic and biological characteristics in different EMT stages remain poorly defined. We conducted an orthotopic mouse (4T1) model of breast cancer to isolate CTCs and identified two phenotypes of CTCs: intermediate E/M and mesenchymal CTCs. MTT, Colony formation, Transwell migration and invasion assays were utilized to examined cell proliferation, colony forming, migration and invasion ability. Both the intermediate E/M and mesenchymal CTCs exhibited lower rates of proliferation, colony formation and invasion, as compared to primary tumor cells. The mesenchymal CTCs had a higher rate of invasion but lower rates of proliferation and colony formation than the intermediate E/M CTCs. They also exhibited lower rates of growth and metastasis than the primary tumor cells in vivo, but the mesenchymal CTCs had a higher rate of metastasis than the intermediate E/M CTCs. Fluid shear stress induced the EMT transition of CTCs. The comprehensive analysis of CTCs proteomics discovered proteins that differentially expressed in the two types of CTCs and their primary tumor cells.