Single Cell Mechanotype and Associated Molecular Changes in Urothelial Cell Transformation and Progression.
Single Cell Mechanotype and Associated Molecular Changes in Urothelial Cell Transformation and Progression.
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DOI：
10.3389/fcell.2020.601376
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发表时间：
2020
影响因子：
5.5
通讯作者：
Rao J
中科院分区：
文献类型：
--
作者：
Yu W;Lu QY;Sharma S;Ly C;Di Carlo D;Rowat AC;LeClaire M;Kim D;Chow C;Gimzewski JK;Rao J
癌细胞机械型改变是新发现的癌症表型事件，而转移性癌细胞表现为细胞硬度降低，变形能力增强。为了进一步研究肿瘤转化和进展早期细胞机制的改变，采用体外多步人尿路上皮细胞致癌模型，分别使用单细胞原子力显微镜、基于微流控的变形能力细胞术和定量变形能力细胞术测量细胞的杨氏模数、变形性和渡越时间。在转化过程中，僵硬、变形性和细胞转运时间的可测量的细胞机械型变化发生在早期。随着细胞从正常细胞到侵袭前细胞，再到侵袭细胞，杨氏硬度模数逐渐降低，而变形性逐渐增加。这些变化在三维培养的微肿瘤肿块和直接来自患者的尿液脱落细胞中得到证实。利用基因筛选和蛋白质组学方法，我们发现与细胞机械型改变有关的主要分子途径似乎是上皮细胞向间质细胞的转变。
Cancer cell mechanotype changes are newly recognized cancer phenotypic events, whereas metastatic cancer cells show decreased cell stiffness and increased deformability relative to normal cells. To further examine how cell mechanotype changes in early stages of cancer transformation and progression, an in vitro multi-step human urothelial cell carcinogenic model was used to measure cellular Young’s modulus, deformability, and transit time using single-cell atomic force microscopy, microfluidic-based deformability cytometry, and quantitative deformability cytometry, respectively. Measurable cell mechanotype changes of stiffness, deformability, and cell transit time occur early in the transformation process. As cells progress from normal, to preinvasive, to invasive cells, Young’s modulus of stiffness decreases and deformability increases gradually. These changes were confirmed in three-dimensional cultured microtumor masses and urine exfoliated cells directly from patients. Using gene screening and proteomics approaches, we found that the main molecular pathway implicated in cell mechanotype changes appears to be epithelial to mesenchymal transition.
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DOI：
10.1158/1078-0432.ccr-14-1215
发表时间：
2015-10-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kim J;Akbani R;Creighton CJ;Lerner SP;Weinstein JN;Getz G;Kwiatkowski DJ
通讯作者：
Kwiatkowski DJ
影响因子：
3.5
作者：
Cross, Sarah E.;Jin, Yu-Sheng;Gimzewski, James K.
通讯作者：
Gimzewski, James K.
影响因子：
3.5
作者：
Cross SE;Jin YS;Lu QY;Rao J;Gimzewski JK
通讯作者：
Gimzewski JK
影响因子：
9.7
作者：
Darling EM;Di Carlo D
通讯作者：
Di Carlo D
DOI：
10.1016/j.pbiomolbio.2014.06.009
发表时间：
2014-08
影响因子：
3.8
作者：
Fedorchak GR;Kaminski A;Lammerding J
通讯作者：
Lammerding J