Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation

Dinah Loerke, Quint Le Duc, Iris Blonk, Andre Kerstens, Emma Spanjaard, Matthias Machacek, Gaudenz Danuser, Johan De Rooij

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

The scattering of cultured epithelial cells in response to hepatocyte growth factor (HGF) is a model system that recapitulates key features of metastatic cell behavior in vitro, including disruption of cell-cell adhesions and induction of cell migration. We have developed image analysis tools that do not require fluorescence tagging and that automatically track and characterize three aspects of scattering in live cells: increase in cell motility, loss of cell-cell adhesion, and spatial dispersion of cells (the redistribution of cells during scattering). We used these tools to screen a library of drugs, and we identified several efficient inhibitors of scattering, which we classified as selective inhibitors of either motility or loss of cell-cell adhesion, or as nonselective inhibitors. We validated the inhibitors and putative targets from this screen in two unrelated model cell lines. Using pharmacological treatments and RNA interference (RNAi), we found that nonsteroidal anti-inflammatory drugs inhibited cell-cell dissociation, that indirubins inhibited cell motility, and that cyclin-dependent kinase 1 and ribosomal S6 kinase were signaling intermediates in HGF-induced cell scattering. This assay is suitable for larger-scale screenings of chemical compounds or RNAi libraries.

Original languageEnglish (US)
Article numberrs5
JournalScience Signaling
Volume5
Issue number231
DOIs
StatePublished - Jul 3 2012

Fingerprint

Cell Movement
Epithelial Cells
Scattering
Cell adhesion
Imaging techniques
Hepatocyte Growth Factor
Cells
Cell Adhesion
CDC2 Protein Kinase
RNA
Ribosomal Protein S6 Kinases
Chemical compounds
RNA Interference
Pharmaceutical Preparations
Image analysis
Assays
Screening
Anti-Inflammatory Agents
Fluorescence
Libraries

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Loerke, D., Le Duc, Q., Blonk, I., Kerstens, A., Spanjaard, E., Machacek, M., ... De Rooij, J. (2012). Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation. Science Signaling, 5(231), [rs5]. https://doi.org/10.1126/scisignal.2002677

Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation. / Loerke, Dinah; Le Duc, Quint; Blonk, Iris; Kerstens, Andre; Spanjaard, Emma; Machacek, Matthias; Danuser, Gaudenz; De Rooij, Johan.

In: Science Signaling, Vol. 5, No. 231, rs5, 03.07.2012.

Research output: Contribution to journalArticle

Loerke, Dinah ; Le Duc, Quint ; Blonk, Iris ; Kerstens, Andre ; Spanjaard, Emma ; Machacek, Matthias ; Danuser, Gaudenz ; De Rooij, Johan. / Quantitative imaging of epithelial cell scattering identifies specific inhibitors of cell motility and cell-cell dissociation. In: Science Signaling. 2012 ; Vol. 5, No. 231.
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