Changing cell mechanics—a precondition for malignant transformation of oral squamous carcinoma cells

Abstract

Oral squamous cell carcinomas (OSCC) are the 6 th most common cancer and the diagnosis is often belated for a curative treatment. The reliable and early differentiation between healthy and diseased cells is the main aim of this study in order to improve the quality of the treatment and to understand tumour pathogenesis.Here, the optical stretcher is used to analyse mechanical properties of cells and their potential to serve as a marker for malignancy. Stretching experiments revealed for the first time that cells of primary OSCCs were deformed by 2.9 % rendering them softer than cells of healthy mucosa which were deformed only by 1.9 %. Furthermore, the relaxation behaviour of the cells revealed that these malignant cells exhibit a faster contraction than their benign counterparts. This suggests that deformability as well as relaxation behaviour can be used as distinct parameters to evaluate emerging differences between these benign and malignant cells. Since many studies in cancer research are performed with cancer cell lines rather than primary cells, we have compared the deformability and relaxation of both types, showing that long time culturing leads to softening of cells. The higher degree of deformability and relaxation behaviour can enable cancer cells to traverse tissue emphasizing that changes in cell architecture may be a potential precondition for malignant transformation. Respecting the fact that even short culture times have an essential effect on the significance of the results, the use of primary cells for further research is recommended. The distinction between malignant and benign cells would enable an early confirmation of cancer diagnoses by testing cell samples of suspect oral lesions.

The Small GTPase Rac1 Increases Cell Surface Stiffness and Enhances 3D Migration Into Extracellular Matrices

“…We not only found an increased cellular deformability in Rac1 −/− cell clones compared to Rac1 fl/fl cells, but Rac removal also caused severely decreased invasion. Our results thus contrast with several other studies reporting that the invasiveness of specific cancer cells is increased when the deformability is increased 47,50,62,63,74 . However, there are other studies that agree with our results, since they show increased deformability (decreased stiffness) and decreased invasiveness of distinct cancer cells and fibroblasts 43,56,57,69 .…”

“…However, there are other studies that agree with our results, since they show increased deformability (decreased stiffness) and decreased invasiveness of distinct cancer cells and fibroblasts 43,56,57,69 . It is worth asking whether these apparently contradictory findings may be explained by the use of distinct methodology, in particular since softness or stiffness of cancer cells has been determined with either optical cell stretcher (adhesion-independent) 47,62,63,74 , magnetic tweezer (adhesion-dependent) 43,56,57,73 or AFM (both adhesion-dependent and -independent) 50 . However, cancer cells frequently appeared to display increased invasiveness if they were softer, in a fashion independent of how softness was measured, i.e.…”

“…However, cancer cells frequently appeared to display increased invasiveness if they were softer, in a fashion independent of how softness was measured, i.e. with optical cell stretcher 47,62,63,74 or AFM, at least when used on suspended cells 50 . In contrast, if AFM measurements were performed with adherent cancer cells, differences in softness between differentially invasive tumor cell lines were abolished 50 .…”

Effect of Nuclear Stiffness on Cell Mechanics and Migration of Human Breast Cancer Cells

“…If the "universal" hypothesis that individual cancer cells are generally softer than non-malignant cells is true (Guck et al, 2005;Cross et al, 2007;Remmerbach et al, 2009;Fritsch et al, 2010;Runge et al, 2014;Lekka, 2016;Meinhövel et al, 2018), MDA-MB-231 cancer cells should be softer than MCF-7 cancer cells, since the MDA-MB-231 cancer cells were more invasive compared to MCF-7 cells. But is the softness of every malignant cancer cell type independent of its biochemical or genetic phenotype fundamentally dependent on different cytoskeletal mechanics or on different nuclear mechanics or on both?…”

“…All of these features contribute to the regulation of cellular motility in 3D confined extracellular matrices. There is still the general hypothesis that cancer cell mechanics contributes "universally" to the 3D migration, as cancer cells with an increased invasive capacity have displayed increased 3D motility and are more deformable and hence softer than cancer cells with a decreased invasive capacity (Guck et al, 2005;Cross et al, 2007;Remmerbach et al, 2009;Fritsch et al, 2010;Runge et al, 2014;Lekka, 2016;Meinhövel et al, 2018). In contrast, it has been hypothesized that a "universal" mechanism for all cancer cell types (Jonietz, 2012;Alibert et al, 2017) or even all cell types (Mierke, 2019b) is probably not suitable for migration into 3D extracellular matrix confinements due to the multiple biochemical and genetic differences among the vastly different cell types.…”