期刊
NANO LETTERS
卷 19, 期 4, 页码 2280-2290出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.nanolett.8b04720
关键词
Cancer cell invasion; mechanobiology; microchannels; confined migration
类别
资金
- Max Planck Institute Postdoctoral Fellowships
- AACR Basic Cancer Research Fellowship [16-40-01-HOLL]
- European Research Council [294852]
- Federal Ministry of Education and Research of Germany
- Max Planck Society
- MWK Baden-Wurttemberg Innovative Projekte (MigChip)
- excellence cluster CellNetworks at the University of Heidelberg
- European Research Council (ERC) [294852] Funding Source: European Research Council (ERC)
Cancer cell invasion through physical barriers in the extracellular matrix (ECM) requires a complex synergy of traction force against the ECM, mechanosensitive feedback, and subsequent cytoskeletal rearrangement. PDMS microchannels were used to investigate the transition from mesenchymal to amoeboid invasion in cancer cells. Migration was faster in narrow 3 mu m-wide channels than in wider 10 mu m channels, even in the absence of cell-binding ECM proteins. Cells permeating narrow channels exhibited blebbing and had smooth leading edge profiles, suggesting an ECM-induced transition from mesenchymal invasion to amoeboid invasion. Live cell labeling revealed a mechanosensing period in which the cell attempts mesenchymal-based migration, reorganizes its cytoskeleton, and proceeds using an amoeboid phenotype. Rho/ROCK (amoeboid) and Rac (mesenchymal) pathway inhibition revealed that amoeboid invasion through confined environments relies on both pathways in at ime- and ECM-dependent manner. This demonstrates that cancer cells can dynamically modify their invasion programming to navigate physically confining matrix conditions.
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