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

Holle, A. W., Devi, N. G. K., Clar, K., Fan, A., Saif, T., Kemkemer, R., et al. (2019). Cancer cells invade confined microchannels via a self-directed mesenchymal-to-amoeboid transition. Nano Letters, 19(4), 2280-2290. doi:10.1021/acs.nanolett.8b04720.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-0E3D-B Version Permalink: http://hdl.handle.net/21.11116/0000-0003-AC36-F
Genre: Journal Article

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 Creators:
Holle, Andrew W.1, 2, Author              
Devi, Neethu Govindan Kutty1, Author              
Clar, Kim1, Author              
Fan, Anthony, Author
Saif, Taher, Author
Kemkemer, Ralf1, Author              
Spatz, Joachim P.1, 2, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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Free keywords: Cancer cell invasion; Mechanobiology; Microchannels, Confined migration
 Abstract: 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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Language(s): eng - English
 Dates: 2019-02-112018-11-232019-02-182019-02-182019
 Publication Status: Published in print
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1021/acs.nanolett.8b04720
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Title: Nano Letters
  Abbreviation : Nano Lett.
Source Genre: Journal
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Publ. Info: Washington, DC : American Chemical Society
Pages: - Volume / Issue: 19 (4) Sequence Number: - Start / End Page: 2280 - 2290 Identifier: ISSN: 1530-6984
CoNE: https://pure.mpg.de/cone/journals/resource/110978984570403