Metastasis contributes to over 90 percent of cancer mortalities and may be influenced by the extracellular matrix (ECM). ECM microenvironments differ in matrix organization, cell-matrix adhesions, and fiber rigidity, which may affect cancer migration and, thus, should be investigated. To understand the interactions between cancer cells and the ECM, we simulate local invasion through ECM organizations of varying determinants. Randomly curved organizations of normal ovarian stroma exhibit minimal local invasion. In contrast, wave-like and parallel linear structures in reorganized ECM organizations provide contact guidance, which increases cancer invasiveness. ECM organizations with strong cell-matrix attachments generate cell pseudopodia, which aid in increasing invasion rate, while weaker attachments prevent the cells from attaching to the fibers and forming pseudopodia, limiting local invasion. ECM organizations with rigid fibers elongate the cell body, allowing them to form cell protrusions and spread rapidly. Conversely, soft fibers stimulate cell rounding and limit migration. Optimizing cell-matrix adhesions and fiber rigidity results in below 10 percent local invasion and reinforces the importance of using computational modeling to discover novel approaches to restricting cancer movement.

中文翻译：

---

操纵细胞外基质组织和参数以控制局部癌症侵袭

转移导致超过 90% 的癌症死亡率，并且可能受到细胞外基质 (ECM) 的影响。ECM 微环境在基质组织、细胞-基质粘附和纤维刚性方面有所不同，这可能会影响癌症迁移，因此应该进行研究。为了了解癌细胞和 ECM 之间的相互作用，我们通过不同决定因素的 ECM 组织模拟局部入侵。正常卵巢基质的随机弯曲组织表现出最小的局部侵袭。相比之下，重组 ECM 组织中的波浪状和平行线性结构提供接触引导，从而增加癌症侵袭性。具有强细胞基质附着的 ECM 组织产生细胞伪足，有助于提高入侵率，而较弱的附着会阻止细胞附着在纤维上并形成伪足，从而限制局部入侵。具有刚性纤维的 ECM 组织拉长了细胞体，使它们形成细胞突起并迅速扩散。相反，软纤维刺激细胞变圆并限制迁移。优化细胞-基质粘附和纤维刚性导致局部侵袭低于 10%，并强调使用计算模型发现限制癌症移动的新方法的重要性。