Naylor Austin, Libmann Maximilian, Raab Izabel, Rappel Wouter-Jan, Sun Bo
Department of Physics, Oregon State University, Corvallis, Oregon 97331, USA.
Department of Biophysics and Biochemistry, Oregon State University, Corvallis, Oregon 97331, USA.
PRX Life. 2024 Dec;2(4). doi: 10.1103/prxlife.2.043022. Epub 2024 Dec 24.
The metastasis of solid tumors hinges on cancer cells navigating through complex three-dimensional tissue environments, characterized by mechanical heterogeneity and biological diversity. This process is closely linked to the dynamic migration behavior exhibited by cancer cells, which dictates the invasiveness of tumors. In our study, we investigate tumor spheroids composed of breast cancer cells embedded in three-dimensional (3D) collagen matrices. Through a combination of quantitative experiments, artificial-intelligence-driven image processing, and mathematical modeling, we uncover rapid transitions in cell phenotypes and phenotype-dependent motility among disseminating cells originating from tumor spheroids. Persistent invasion leads to continuous remodeling of the extracellular matrix surrounding the spheroids, altering the landscape of migration phenotypes. Consequently, filopodial cells emerge as the predominant phenotype across diverse extracellular matrix conditions. Our findings unveil the complex mesoscale dynamics of invading tumor spheroids, shedding light on the complex interplay between migration phenotype plasticity, microenvironment remodeling, and cell motility within 3D extracellular matrices.
实体瘤的转移取决于癌细胞在复杂的三维组织环境中穿行，这种环境具有机械异质性和生物多样性。这一过程与癌细胞表现出的动态迁移行为密切相关，而这种行为决定了肿瘤的侵袭性。在我们的研究中，我们研究了由嵌入三维（3D）胶原基质中的乳腺癌细胞组成的肿瘤球体。通过定量实验、人工智能驱动的图像处理和数学建模相结合的方法，我们发现源自肿瘤球体的播散细胞中存在细胞表型的快速转变以及表型依赖性运动。持续的侵袭导致球体周围细胞外基质的持续重塑，改变了迁移表型的格局。因此，丝状伪足细胞在各种细胞外基质条件下成为主要表型。我们的研究结果揭示了侵袭性肿瘤球体复杂的中尺度动力学，阐明了三维细胞外基质中迁移表型可塑性、微环境重塑和细胞运动之间的复杂相互作用。
