Wong Ian Y, Javaid Sarah, Wong Elisabeth A, Perk Sinem, Haber Daniel A, Toner Mehmet, Irimia Daniel
1] BioMEMS Resource Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA [2].
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Nat Mater. 2014 Nov;13(11):1063-71. doi: 10.1038/nmat4062. Epub 2014 Aug 17.
During cancer progression, malignant cells in the tumour invade surrounding tissues. This transformation of adherent cells to a motile phenotype has been associated with the epithelial-mesenchymal transition (EMT). Here, we show that EMT-activated cells migrate through micropillar arrays as a collectively advancing front that scatters individual cells. Individual cells with few neighbours dispersed with fast, straight trajectories, whereas cells that encountered many neighbours migrated collectively with epithelial biomarkers. We modelled these emergent dynamics using a physical analogy to phase transitions during binary-mixture solidification, and validated it using drug perturbations, which revealed that individually migrating cells exhibit diminished chemosensitivity. Our measurements also indicate a degree of phenotypic plasticity as cells interconvert between individual and collective migration. The study of multicellular behaviours with single-cell resolution should enable further quantitative insights into heterogeneous tumour invasion.
在癌症进展过程中,肿瘤中的恶性细胞会侵入周围组织。贴壁细胞向运动性表型的这种转变与上皮-间质转化(EMT)有关。在这里,我们表明,EMT激活的细胞通过微柱阵列迁移,形成一个集体前进的前沿,该前沿会分散单个细胞。与少数邻居接触的单个细胞以快速、直线轨迹分散,而遇到许多邻居的细胞则与上皮生物标志物一起集体迁移。我们使用二元混合物凝固过程中相变的物理类比来模拟这些涌现动力学,并使用药物扰动对其进行验证,结果表明单独迁移的细胞表现出较低的化学敏感性。我们的测量还表明,随着细胞在个体迁移和集体迁移之间相互转换,存在一定程度的表型可塑性。以单细胞分辨率研究多细胞行为应能进一步定量洞察异质性肿瘤侵袭。