Shen Yang, Schmidt B U Sebastian, Kubitschke Hans, Morawetz Erik W, Wolf Benjamin, Käs Josef A, Losert Wolfgang
1Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742 USA.
2Peter Debye Institute for Soft Matter Physics, Leipzig University, Linnéstr. 5, 04103 Leipzig, Germany.
Cancer Converg. 2020;4(1):1. doi: 10.1186/s41236-020-0010-1. Epub 2020 Feb 3.
Cellular heterogeneity in tumor cells is a well-established phenomenon. Genetic and phenotypic cell-to-cell variability have been observed in numerous studies both within the same type of cancer cells and across different types of cancers. Another known fact for metastatic tumor cells is that they tend to be softer than their normal or non-metastatic counterparts. However, the heterogeneity of mechanical properties in tumor cells are not widely studied.
Here we analyzed single-cell optical stretcher data with machine learning algorithms on three different breast tumor cell lines and show that similar heterogeneity can also be seen in mechanical properties of cells both within and between breast tumor cell lines. We identified two clusters within MDA-MB-231 cells, with cells in one cluster being softer than in the other. In addition, we show that MDA-MB-231 cells and MDA-MB-436 cells which are both epithelial breast cancer cell lines with a mesenchymal-like phenotype derived from metastatic cancers are mechanically more different from each other than from non-malignant epithelial MCF-10A cells.
Since stiffness of tumor cells can be an indicator of metastatic potential, this result suggests that metastatic abilities could vary within the same monoclonal tumor cell line.
肿瘤细胞中的细胞异质性是一种已被充分证实的现象。在众多研究中，无论是在同一类型的癌细胞内还是在不同类型的癌症之间，都观察到了基因和表型的细胞间变异性。另一个关于转移性肿瘤细胞的已知事实是，它们往往比正常或非转移性对应细胞更柔软。然而，肿瘤细胞力学特性的异质性尚未得到广泛研究。
在此，我们使用机器学习算法分析了三种不同乳腺肿瘤细胞系的单细胞光镊数据，结果表明，在乳腺肿瘤细胞系内部和之间的细胞力学特性中也能观察到类似的异质性。我们在MDA-MB-231细胞中识别出两个簇，其中一个簇中的细胞比另一个簇中的细胞更柔软。此外，我们还表明，MDA-MB-231细胞和MDA-MB-436细胞均为具有间充质样表型的转移性上皮性乳腺癌细胞系，它们之间的力学差异比它们与非恶性上皮性MCF-10A细胞之间的差异更大。
由于肿瘤细胞的硬度可能是转移潜能的一个指标，这一结果表明，在同一单克隆肿瘤细胞系中，转移能力可能存在差异。
