Heterotypic contact inhibition of locomotion can drive cell sorting between epithelial and mesenchymal cell populations

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Abstract

Interactions between different cell-types can induce distinct contact inhibition of locomotion (CIL) responses that are hypothesised to control population-wide behaviours during embryogenesis. However, our understanding of the signals that lead to cell-type specific repulsion and the precise capacity of heterotypic CIL responses to drive emergent behaviours is lacking. Using a new model of heterotypic CIL, we show that fibrosarcoma cells, but not fibroblasts, are actively repelled by epithelial cells in culture. We show that knocking down EphB2 or ERK in fibrosarcoma cells specifically leads to disruption of the repulsion phase of CIL in response to interactions with epithelial cells. We also examine the population-wide effects when these various cell combinations are allowed to interact in culture. Unlike fibroblasts, fibrosarcoma cells completely segregate from epithelial cells and inhibiting their distinct CIL response by knocking down EphB2 or ERK also disrupts this emergent sorting behaviour. These data suggest that heterotypic CIL responses, in conjunction with processes such as differential adhesion, may aid the sorting of cell populations.
Original languageEnglish
Article numberjcs223974
JournalJournal of Cell Science
Volume132
Issue number11
Early online date10 May 2019
DOIs
Publication statusE-pub ahead of print - 10 May 2019

Keywords

  • Cell sorting
  • Contact inhibition of locomotion
  • Ephrin signalling
  • ERK signalling
  • MAPK signalling

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