Cancer Cells Invade Confined Microchannels via a Self-Directed Mesenchymal-to-Amoeboid Transition

Andrew W. Holle, Neethu Govindan Kutty Devi, Kim Clar, Anthony Fan, Taher Saif, Ralf Kemkemer, Joachim P. Spatz

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2280-2290
Number of pages11
JournalNano letters
Volume19
Issue number4
DOIs
StatePublished - Apr 10 2019

Keywords

  • Cancer cell invasion
  • confined migration
  • mechanobiology
  • microchannels

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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  • Cite this

    Holle, A. W., Govindan Kutty Devi, N., Clar, K., Fan, A., Saif, T., Kemkemer, R., & Spatz, J. P. (2019). Cancer Cells Invade Confined Microchannels via a Self-Directed Mesenchymal-to-Amoeboid Transition. Nano letters, 19(4), 2280-2290. https://doi.org/10.1021/acs.nanolett.8b04720