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Cancer cells invade confined microchannels via a self-directed mesenchymal-to-amoeboid transition

  • 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 μm-wide channels than in wider 10 μm 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 a time- 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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Metadaten
Name:Kemkemer, Ralf
URN:urn:nbn:de:bsz:rt2-opus4-23924
DOI:https://doi.org/10.1021/acs.nanolett.8b04720
ISSN:1530-6984
eISSN:1530-6992
Erschienen in:Nano letters : a journal dedicated to nanoscience and nanotechnology
Publisher:ACS Publ.
Place of publication:Washington, DC
Document Type:Article
Language:English
Year of Publication:2019
Tag:cancer cell invasion; confined migration; mechanobiology; microchannels
Volume:19
Issue:4
Pagenumber:11
First Page:2280
Last Page:2290
Dewey Decimal Classification:540 Chemie
Open Access:Ja
Licence (German):License Logo  Creative Commons - CC BY - Namensnennung 4.0 International