Detecting heterogeneity in and between breast cancer cell lines

Abstract

Background: 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. Results: 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. Conclusion: 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.

Comparative Study of Transcriptomics-Based Scoring Metrics for the Epithelial-Hybrid-Mesenchymal Spectrum

“…Various attempts to characterize the spectrum of EMT at molecular and/or morphological levels have been made recently, enabled by latest developments in multiplex imaging, single-cell RNAseq and inducible systems (Mandal et al, 2016;Pastushenko et al, 2018;Stylianou et al, 2018;Cook and Vanderhyden, 2019;Devaraj and Bose, 2019;Karacosta et al, 2019;Wang W. et al, 2019;Watanabe et al, 2019;Lam et al, 2020). These approaches have highlighted the dynamical nature of EMT in driving cancer progression in patients (Jolly and Celia-Terrassa, 2019), and the heterogeneity in EMT status in cell lines and patient samples (Panchy et al, 2020;Shen et al, 2020). Further, various approaches to quantify the EMT spectrum of samples based on different signatures of tumor types have been made (Foroutan et al, 2017;Puram et al, 2017).…”

Atomic force microscopy reveals the mechanical properties of breast cancer bone metastases

“…It is thus essential to quantify any differences between the mechanical properties of 3D in vivo/ex vivo tumours and the relevant 2D in vitro cell model, in order to improve research models and hence increase our understanding of the mechanical processes involved in tumour progression. The challenge is exacerbated by the wide variation in Young's moduli determined from the same in vitro cell lines published by different laboratories 5,27,28,29 , making a direct comparison of the properties measured in the current study difficult. Due to likely variations in the same cell-line (e.g.…”

Changes in Biomechanical Properties of A375 Cells Due to the Silencing of TMSB4X Expression Are Not Directly Correlated with Alterations in Their Stemness Features

“…The phenotypic heterogeneity has been reported for several cultured already for decades cell lines, e.g., MDA-MB-231 (breast cancer) [ 80 ], Jurkat and K562 (leukemia) [ 81 ], or HeLa (cervical carcinoma) [ 82 ]. For melanoma cell lines, phenotypic heterogeneity was observed as well.…”