Potomkin Mykhailo, Kim Oleg, Klymenko Yuliya, Alber Mark, Aranson Igor S
Department of Mathematics, University of California, Riverside, Riverside, CA 92521, USA.
Interdisciplinary Center for Quantitative Modeling in Biology, University of California, Riverside, Riverside, CA, USA.
iScience. 2025 Jan 24;28(3):111883. doi: 10.1016/j.isci.2025.111883. eCollection 2025 Mar 21.
Early stages of metastasis depend on the collective behavior of cancer cells and their interaction with the extracellular matrix (ECM). Cancer cell clusters are known to exhibit higher metastatic potential than single cells. To explore clustering dynamics, we developed a calibrated computational model describing how motile cancer cells biochemically and biomechanically interact with the ECM during the initial invasion phase, including ECM degradation and mechanical remodeling. The model reveals that cluster formation time, size, and shape are influenced by ECM degradation rates and cellular compliance to external stresses (durotaxis). The results align with experimental observations, demonstrating distinct cell trajectories and cluster morphologies shaped by biomechanical parameters. The simulations provide valuable insights into cancer invasion dynamics and may suggest potential therapeutic strategies targeting early-stage invasive cells.
转移的早期阶段取决于癌细胞的集体行为及其与细胞外基质（ECM）的相互作用。已知癌细胞簇比单个细胞具有更高的转移潜能。为了探索聚集动力学，我们开发了一个经过校准的计算模型，该模型描述了运动性癌细胞在初始侵袭阶段如何与ECM进行生化和生物力学相互作用，包括ECM降解和机械重塑。该模型表明，簇的形成时间、大小和形状受ECM降解速率以及细胞对外界应力的顺应性（趋硬性）影响。结果与实验观察结果一致，证明了由生物力学参数塑造的不同细胞轨迹和簇形态。这些模拟为癌症侵袭动力学提供了有价值的见解，并可能提示针对早期侵袭性细胞的潜在治疗策略。
