van der Net Anouk, Rahman Zaid, Bordoloi Ankur D, Muntz Iain, Ten Dijke Peter, Boukany Pouyan E, Koenderink Gijsje H
Delft University of Technology, Department of Bionanoscience, Kavli Institute of Nanoscience, Delft 2629 HZ, the Netherlands.
Delft University of Technology, Department of Chemical Engineering, Delft 2629 HZ, the Netherlands.
iScience. 2024 Nov 19;27(12):111424. doi: 10.1016/j.isci.2024.111424. eCollection 2024 Dec 20.
Epithelial-to-mesenchymal transitions (EMT) and unjamming transitions provide two distinct pathways for cancer cells to become invasive, but it is still unclear to what extent these pathways are connected. Here, we addressed this question by performing 3D spheroid invasion assays on epithelial-like (A549) and mesenchymal-like (MV3) cancer cell lines in collagen-based hydrogels, where we varied both the invasive character of the cells and matrix porosity. We found that the onset time of invasion was correlated with the matrix porosity and vimentin levels, while the spheroid expansion rate correlated with MMP1 levels. Spheroids displayed solid-like (non-invasive) states in small-pore hydrogels and fluid-like (strand-based) or gas-like (disseminating cells) states in large-pore hydrogels or for mesenchymal-like cells. Our findings are consistent with different unjamming states as a function of cell motility and matrix confinement predicted in recent models for cancer invasion, but show that cell motility and matrix confinement are coupled via EMT-related matrix degradation.
上皮-间质转化（EMT）和去阻塞转变为癌细胞的侵袭提供了两条不同的途径，但这些途径在多大程度上相互关联仍不清楚。在这里，我们通过在基于胶原蛋白的水凝胶中对上皮样（A549）和间充质样（MV3）癌细胞系进行三维球体侵袭试验来解决这个问题，在该试验中，我们改变了细胞的侵袭特性和基质孔隙率。我们发现侵袭的起始时间与基质孔隙率和波形蛋白水平相关，而球体扩张率与MMP1水平相关。球体在小孔径水凝胶中呈现固态（非侵袭性）状态，在大孔径水凝胶中或对于间充质样细胞呈现液态（基于链状）或气态（扩散细胞）状态。我们的发现与最近癌症侵袭模型中预测的作为细胞运动性和基质限制函数的不同去阻塞状态一致，但表明细胞运动性和基质限制通过与EMT相关的基质降解相互耦合。
