The interface stiffness and topographic feature dictate interfacial invasiveness of cancer spheroids

During cancer metastasis, tumor cells likely navigate, in a collective manner, discrete tissue spaces comprising inherently heterogeneous ECM microstructures where interfaces may be frequently encountered. Studies have shown that cell migration modes can be determined by adaptation to mechanical/topographic cues from interfacial microenvironments. However, less attention has been paid to exploring the impact of interfacial mechnochemical attributes on invasive and metastatic behaviors of tumor aggregates. Here, we excogitated a collagen matrix-solid substrate interface platform to investigate the afore-stated interesting issue. Our data revealed that stiffer interfaces stimulated spheroid outgrowth by motivating detachment of single cells and boosting their motility and velocity. However, stronger interfacial adhesive strength between matrix and substrate led to the opposite outcomes. Besides, this interfacial parameter also affected the morphological switch between migration modes of the detached cells and their directionality. Mechanistically, myosin II-mediated cell contraction, compared to MMPs-driven collagen degradation, was shown to play a more crucial role in the invasive outgrowth of tumor spheroids in interfacial microenvironments. Thus, our findings highlight the importance of heterogeneous interfaces in addressing and combating cancer metastasis.
Cell line: MDA-MB-231
Z: microscope plane
T: Time point (T1 to T144, each time point 10 minutes in 24 hours)
The experiment protocol can be found in our paper: https://iopscience.iop.org/article/10.1088/1758-5090/acaa00

在癌症转移过程中，肿瘤细胞可能以集体方式在由本质上异质性的细胞外基质微结构组成的离散组织空间中导航，其中界面可能频繁遭遇。研究表明，细胞迁移模式可以通过适应界面微环境中的机械/拓扑线索来确定。然而，对于界面机械化学属性对肿瘤团块侵袭性和转移行为的影响，关注相对较少。在本研究中，我们构思了一种胶原蛋白基质-固体基底界面平台，以探究上述有趣问题。我们的数据表明，较硬的界面通过激发单个细胞的脱落并增强其运动性和速度来刺激球形体的生长。然而，基质与基底之间更强的界面粘附力导致了相反的结果。此外，这一界面参数还影响了脱落细胞迁移模式之间的形态学转换及其方向性。机制上，与MMPs驱动的胶原蛋白降解相比，肌球蛋白II介导的细胞收缩在界面微环境中肿瘤球形体的侵袭性生长中显示出更为关键的作用。因此，我们的发现突出了异质界面在应对和对抗癌症转移中的重要性。
细胞系：MDA-MB-231
Z：显微镜平面
T：时间点（T1至T144，每24小时10分钟一次）
实验方案可在我方论文中找到：https://iopscience.iop.org/article/10.1088/1758-5090/acaa00