Li Fenfang, Cima Igor, Vo Jess Honganh, Tan Min-Han, Ohl Claus Dieter
Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 11 Mandalay Road,Singapore 308232, Singapore.
Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University Singapore, 21 Nanyang Link, Singapore 637371, Singapore.
Micromachines (Basel). 2020 May 9;11(5):486. doi: 10.3390/mi11050486.
Deformability is shown to correlate with the invasiveness and metastasis of cancer cells. Recent studies suggest epithelial-to-mesenchymal transition (EMT) might enable cancer metastasis. However, the correlation of EMT with cancer cell deformability has not been well elucidated. Cellular deformability could also help evaluate the drug response of cancer cells. Here, we combine hydrodynamic stretching and microsieve filtration to study cellular deformability in several cellular models. Hydrodynamic stretching uses extensional flow to rapidly quantify cellular deformability and size with high throughput at the single cell level. Microsieve filtration can rapidly estimate relative deformability in cellular populations. We show that colorectal cancer cell line RKO with the mesenchymal-like feature is more flexible than the epithelial-like HCT116. In another model, the breast epithelial cells MCF10A with deletion of the TP53 gene are also significantly more deformable compared to their isogenic wildtype counterpart, indicating a potential genetic link to cellular deformability. We also find that the drug docetaxel leads to an increase in the size of A549 lung cancer cells. The ability to associate mechanical properties of cancer cells with their phenotypes and genetics using single cell hydrodynamic stretching or the microsieve may help to deepen our understanding of the basic properties of cancer progression.
结果表明，细胞变形能力与癌细胞的侵袭性和转移相关。最近的研究表明，上皮-间质转化（EMT）可能促使癌症转移。然而，EMT与癌细胞变形能力之间的相关性尚未得到充分阐明。细胞变形能力也有助于评估癌细胞的药物反应。在此，我们结合流体动力拉伸和微筛过滤技术，在几种细胞模型中研究细胞变形能力。流体动力拉伸利用拉伸流在单细胞水平上以高通量快速量化细胞变形能力和大小。微筛过滤可以快速估计细胞群体中的相对变形能力。我们发现，具有间充质样特征的结肠癌细胞系RKO比上皮样的HCT116更具柔韧性。在另一个模型中，与同基因野生型对应物相比，缺失TP53基因的乳腺上皮细胞MCF10A的变形能力也显著更强，这表明细胞变形能力可能存在潜在的遗传联系。我们还发现，多西他赛药物会导致A549肺癌细胞体积增大。利用单细胞流体动力拉伸或微筛技术将癌细胞的力学特性与其表型和遗传学联系起来的能力，可能有助于加深我们对癌症进展基本特性的理解。
