Liu Huiqing, Wang Nan, Zhang Zhe, Wang Hongda, Du Jun, Tang Jilin
State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
University of Chinese Academy of Sciences, Beijing, China.
Scanning. 2017 Jun 21;2017:2027079. doi: 10.1155/2017/2027079. eCollection 2017.
Chronic inflammation orchestrates the tumor microenvironment and is strongly associated with cancer. Tumor necrosis factor- (TNF) is involved in tumor invasion and metastasis by inducing epithelial to mesenchymal transition (EMT). This process is defined by the loss of epithelial characteristics and gain of mesenchymal traits. The mechanisms of TNF-induced EMT in cancer cells have been well studied. However, mechanical properties have not yet been probed. In this work, atomic force microscopy (AFM) was applied to investigate the morphology and mechanical properties of EMT in HCT116 human colon cancer cells. A remarkable morphological change from cobblestone shape to spindle-like morphology was observed. In parallel, AFM images showed that the cellular cytoskeleton was rearranged from a cortical to a stress-fiber pattern. Moreover, cell stiffness measurements indicated that Young's modulus of cells gradually reduced from 1 to 3 days with TNF-treatment, but it has an apparent increase after 4 days of treatment compared with that for 3 days. Additionally, Young's modulus of the cells treated with TNF for 4 days is slightly larger than that for 1 or 2 days, but still less than that of the untreated cells. Our work contributes to a better understanding of colorectal cancer metastasis induced by inflammation.
慢性炎症调控肿瘤微环境,且与癌症密切相关。肿瘤坏死因子(TNF)通过诱导上皮-间质转化(EMT)参与肿瘤侵袭和转移。这一过程以上皮特征丧失和间质特性获得为特征。TNF诱导癌细胞发生EMT的机制已得到充分研究。然而,其力学特性尚未得到探究。在这项研究中,应用原子力显微镜(AFM)来研究HCT116人结肠癌细胞中EMT的形态和力学特性。观察到细胞形态从鹅卵石状显著转变为纺锤状。同时,AFM图像显示细胞骨架从皮质模式重排为应力纤维模式。此外,细胞硬度测量表明,经TNF处理1至3天,细胞的杨氏模量逐渐降低,但与处理3天时相比,处理4天后明显增加。另外,经TNF处理4天的细胞的杨氏模量略大于处理1天或2天的细胞,但仍低于未处理细胞。我们的工作有助于更好地理解炎症诱导的结直肠癌转移。