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Confinement, Jamming, and Adhesion in Cancer Cells Dissociating from a Collectively Invading Strand.

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Cancer cell dissociation during invasion, leading to metastasis, is controlled by cell states and adhesion. Leader cells promote single-cell detachment, while strong cell-cell adhesion results in larger, fewer ruptures.

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Area of Science:

  • Biophysics
  • Cancer Biology
  • Cellular Mechanics

Background:

  • Tumor invasion and metastasis involve cancer cells breaking away from the primary tumor.
  • Understanding the mechanisms controlling cell dissociation is crucial for predicting metastatic potential.

Purpose of the Study:

  • To investigate the factors controlling cancer cell dissociation during invasion.
  • To determine if cell-cell adhesion and chemotactic cues influence single-cell versus group dissociation.

Main Methods:

  • Developed a physical model based on experiments using microfluidic devices with varying microchannel widths.
  • Employed a phase-field cell motility model incorporating three distinct cell states: follower, guided, and leader cells.
  • Analyzed the impact of cell-channel adhesion, cell-cell adhesion, and chemotaxis on cell dissociation.

Main Results:

  • Most dissociation events involved single cells, with larger group ruptures observed in wider channels.
  • Rupture probability was largely independent of channel width.
  • Cell-channel adhesion was essential for invasion in narrow channels; strong cell-cell adhesion led to fewer, larger ruptures.
  • Strong chemotaxis promoted larger and faster ruptures.
  • Cellular unjamming was identified as necessary but not sufficient for rupture.

Conclusions:

  • A physical model with leader cells successfully recapitulates experimental observations of cancer cell dissociation.
  • Cell-cell adhesion and chemotaxis significantly influence the size and frequency of cell ruptures during invasion.
  • These findings provide insights into the physical mechanisms driving metastasis.