转录组特征分析、乳腺癌细胞自发 EMT/MET 转化的化疗敏感性及调控作用的外泌体研究。
Transcriptomic Characterization, Chemosensitivity and Regulatory Effects of Exosomes in Spontaneous EMT/MET Transitions of Breast Cancer Cells.
机构信息
Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section of Pharmacology and Toxicology, University of Florence, Florence, Italy
Department of Neuroscience, Psychology, Drug Research and Child Health - NEUROFARBA - Section of Pharmacology and Toxicology, University of Florence, Florence, Italy.
出版信息
Cancer Genomics Proteomics. 2019 May-Jun;16(3):163-173. doi: 10.21873/cgp.20122.
BACKGROUND/AIM: We examined the gene expression changes of breast cancer cells spontaneously undergoing epithelial-mesenchymal transition (EMT) and its reverse process mesenchymal-epithelial transition (MET) and the role of exosomes in these transitions.
MATERIALS AND METHODS
Highly invasive mesenchymal-like breast cancer cells, MDA-MB-231 (basal cells), EMT and MET variants, were characterized by microarray gene expression profiling, immunocytochemistry and chemo-sensitivity.
RESULTS
Spontaneously disseminated cells were anoikis resistant, exhibited a dissociative, EMT-like phenotype and underwent MET when reseeded in cell-free plates. MET was inhibited by exosomes secreted by basal cells. Chemo-sensitivity to doxorubicin, vincristine and paclitaxel decreased in the order EMT<MET<basal. Phenotypic plasticity arose with differential expression of metastasis and stemness associated genes (LGR5, FZD10, DTX1, ErbB3, FTH1 and DLL4) and pathways (DNA replication and repair, ABC transporter, Hedgehog, Notch and metabolic pathways).
CONCLUSION
This is an appropriate model for studying EMT/MET transitions, drug targets and the role of exosomes in breast cancer dissemination.
背景/目的：我们研究了自发发生上皮-间充质转化（EMT）及其逆转过程间充质-上皮转化（MET）的乳腺癌细胞的基因表达变化，以及外泌体在这些转化中的作用。
材料和方法
高度侵袭性的间充质样乳腺癌细胞 MDA-MB-231（基底细胞），通过微阵列基因表达谱分析、免疫细胞化学和化疗敏感性进行 EMT 和 MET 变体的特征分析。
结果
自发扩散的细胞对失巢凋亡具有抗性，表现出离散的 EMT 样表型，并在无细胞平板中重新接种时发生 MET。基底细胞分泌的外泌体抑制 MET。多柔比星、长春新碱和紫杉醇的化疗敏感性依次降低 EMT<MET<基底。与转移和干性相关的基因（LGR5、FZD10、DTX1、ErbB3、FTH1 和 DLL4）和途径（DNA 复制和修复、ABC 转运体、Hedgehog、Notch 和代谢途径）的差异表达导致表型可塑性的出现。
结论
这是研究 EMT/MET 转化、药物靶点和外泌体在乳腺癌扩散中的作用的合适模型。
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