In homoeostasis, the shape and sessility of untransformed epithelial cells are intricately linked together. Variations of this relationship in migrating cancer cells as they encounter different microenvironments are as yet ill understood. Here, we explore the interdependency of such traits in two morphologically distinct invasive ovarian cancer cell lines (OVCAR-3 and SK-OV-3) under mechanically variant contexts. We first established a metric toolkit that assessed traits associated with cell motion and shape, and rigorously measured their dynamical variation across trajectories of migration using a Shannon entropic distribution. Two stiffness conditions on polymerized collagen I with Young’s moduli of 0.5 kPa (soft) and 20 kPa (stiff) were chosen. Both the epithelioid OVCAR-3 and mesenchymal SK-OV-3 cells on soft substrata exhibited slow and undirected migration. On stiff substrata, SK-OV-3 showed faster persistent directed motion. Surprisingly, OVCAR-3 cells on stiffer substrata moved even faster than SK-OV-3 cells but showed a distinct angular motion. The polarity of SK-OV-3 cells on stiff substrata was well correlated with their movement, whereas, for OVCAR-3, we observed an unusual “slip” behavior, wherein the axes of cell shape and movement were poorly correlated. Whereas SK-OV-3 and OVCAR-3 showed greater mean deformation on stiffer substrata, the latter was anticorrelated with variation in angular motion or the mean deviation between shape and motility axis for SK-OV-3 but poorly correlated for OVCAR-3. Moreover, on softer substrata OVCAR-3 and SK-OV-3 were relatively rigid but showed greater shape variation (with OVCAR-3 showing a higher fold change) on stiffer substrata. Our findings suggest that greater deformability on stiffer milieu allow epithelioid cells to overcome constraints on the congruence in axis of shape and motion seen for mesenchymal cells and display distinct motile behaviors across this phenotypic spectrum.

中文翻译：

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卵巢癌细胞在坚硬的胶原基质上表现出不同的迁移策略


在匀态中，未转化的上皮细胞的形状和无柄错综复杂地联系在一起。目前尚不清楚迁移的癌细胞在遇到不同微环境时这种关系的变化。在这里，我们探讨了在机械变异背景下两种形态不同的侵袭性卵巢癌细胞系（OVCAR-3 和 SK-OV-3）中这些性状的相互依赖性。我们首先建立了一个度量工具包，用于评估与细胞运动和形状相关的特征，并使用香农熵分布严格测量它们在迁移轨迹上的动态变化。选择了两种聚合物胶原 I 的刚度条件，杨氏模量为 0.5 kPa（软）和 20 kPa（硬）。软基质上的上皮样 OVCAR-3 和间充质 SK-OV-3 细胞均表现出缓慢且无方向的迁移。在坚硬的底层上，SK-OV-3 表现出更快的持续定向运动。令人惊讶的是，较硬基质上的 OVCAR-3 细胞移动速度甚至比 SK-OV-3 细胞更快，但表现出明显的角运动。SK-OV-3 细胞在坚硬基质上的极性与它们的运动密切相关，而对于 OVCAR-3，我们观察到一种不寻常的“滑动”行为，其中细胞形状和运动的轴相关性很差。虽然 SK-OV-3 和 OVCAR-3 在较硬的底层上显示出更大的平均变形，但后者与 SK-OV-3 的角运动变化或形状和运动轴之间的平均偏差呈负相关，但与 OVCAR-3 的相关性差。此外，在较软的基质上，OVCAR-3 和 SK-OV-3 相对坚硬，但在较硬的基质上表现出更大的形状变化 （OVCAR-3 显示出更高的倍数变化）。 我们的研究结果表明，在较硬的环境中具有更大的变形能力，使上皮样细胞能够克服间充质细胞的形状和运动轴一致性的限制，并在该表型谱中表现出不同的运动行为。