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Related Experiment Videos

Integrin alpha3beta1 engagement disrupts intercellular adhesion.

K Kawano1, S S Kantak, M Murai

  • 1Department of Stomatology, University of California at San Francisco, San Francisco, California, 94143-0512, USA.

Experimental Cell Research
|January 5, 2001
PubMed
Summary
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Epithelial cell rearrangements, crucial for tissue development and cancer spread, are triggered by beta1 integrin activation. Specific integrin-ECM interactions, like laminin 5, promote cell dispersion, mimicking epithelial-mesenchymal transitions.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Cancer Biology

Background:

  • Epithelial cells undergo rearrangements during tissue morphogenesis and tumor invasion.
  • These rearrangements involve repositioning cells relative to each other and the extracellular matrix (ECM).

Purpose of the Study:

  • To investigate how beta1 integrins and ECM interactions regulate intercellular rearrangements in epithelial cells.
  • To understand the molecular mechanisms underlying epithelial morphogenesis and tumor invasion.

Main Methods:

  • Utilized three-dimensional multicellular aggregates (MCAs) of squamous epithelial cells.
  • MCAs were cultured on various substrates including collagen type I, fibronectin, laminin 1, and a specific epithelial-derived matrix.
  • Analyzed cell-cell adhesion dynamics, E-cadherin levels, integrin activation, and cytoskeletal organization (F-actin, microspikes, fascin).

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Main Results:

  • Activation of beta1 integrins by ECM ligation triggered intercellular rearrangements.
  • MCAs formed compact spheroids on non-adherent substrates, with E-cadherin levels increasing due to enhanced stability.
  • Seeding MCAs on an epithelial-derived matrix containing laminin 5 induced cell attachment, spreading, loss of cell-cell junctions, and dispersion, requiring alpha3beta1 integrin.
  • Substrate-immobilized anti-integrin antibodies mimicked the dispersion induced by laminin 5.
  • Cells on laminin 5 exhibited F-actin, microspikes, and fascin accumulation, indicative of an epithelial-mesenchymal-like transition.

Conclusions:

  • Specific integrin-ligand engagements regulate cadherin-based cell-cell adhesions.
  • These processes are critical for both normal epithelial morphogenesis and pathological tumor invasion.
  • The findings highlight the role of integrins in mediating cell behavior during dynamic tissue remodeling.