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Related Experiment Videos

Tumor cell invasiveness correlates with changes in integrin expression and localization.

Sabine Maschler1, Gerhard Wirl, Herbert Spring

  • 1Research Institute of Molecular Pathology, Dr Bohrgasse 7, Vienna 1030, Austria. maschler@imp.univie.ac.at

Oncogene
|February 3, 2005
PubMed
Summary

Transforming growth factor-beta (TGFbeta1) induces epithelial-mesenchymal transition (EMT) in Ras-transformed cells, promoting migration. The alpha5beta1 integrin plays a key role in this EMT process and cell migration during tumor progression.

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Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Transforming growth factor-beta (TGFbeta1) induces cell cycle arrest in normal mammary epithelial cells (EpH4).
  • However, TGFbeta1 triggers epithelial-mesenchymal transition (EMT) in Ha-Ras-transformed EpH4 cells (EpRas), leading to a mesenchymal phenotype (FibRas).
  • EMT is associated with advanced tumor stages and increased cell migration.

Purpose of the Study:

  • To investigate the role of integrins in TGFbeta1-induced EMT.
  • To understand the changes in cell adhesion and integrin expression during EMT.
  • To identify key integrins involved in the migratory behavior of EpRas and FibRas cells.

Main Methods:

  • Analysis of cell adhesion to extracellular matrix components.

Related Experiment Videos

  • Assessment of integrin subunit expression via Western blotting or similar techniques.
  • Inhibition of integrin function using function-blocking antibodies in 3D culture models.

    • Main Results:

    • EpRas and FibRas cells exhibited increased adhesion to fibronectin, collagens I/IV, and laminin 1.
    • Ras transformation enhanced or induced expression of integrin subunits beta1, alpha2, alpha3, alpha5, and alpha6, with alpha5 and alpha6 upregulated in FibRas cells.
    • Polarized EpRas cells showed distinct integrin localization, while FibRas cells displayed widespread co-expression of alpha5beta1 and alpha6 integrins.
    • Formation of alpha5beta1 complexes and fibronectin deposition occurred during EMT.
    • Alpha5beta1 integrin blockade inhibited migration and induced apoptosis in EpRas cells during EMT in collagen gels.

    Conclusions:

    • Functional alpha5beta1 integrin is crucial for TGFbeta1-induced EMT.
    • Mesenchymal integrins like alpha5beta1 replace previously functional integrins such as alpha6beta4 after EMT.
    • These findings highlight the role of specific integrins in mediating cell migration and survival during tumor progression.