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Fibronectin matrix assembly enhances adhesion-dependent cell growth

J Sottile1, D C Hocking, P J Swiatek

  • 1Department of Physiology and Cell Biology (A-134), Neil Hellman Medical Research Building, Albany Medical College, Albany, NY 12208, USA. jsottile@ccgateway.amc.edu.

Journal of Cell Science
|September 10, 1998
PubMed
Summary

Fibronectin polymerization in the extracellular matrix significantly enhances cell growth. This process is crucial for adhesion-dependent cell proliferation, independent of integrin clustering alone.

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Area of Science:

  • Cell Biology
  • Biochemistry
  • Extracellular Matrix Research

Background:

  • Cell growth regulation involves interactions with the extracellular matrix (ECM).
  • Altered fibronectin deposition in the ECM can contribute to fibrosis and atherosclerosis.
  • Fibronectin's role in cell proliferation and migration is critical for wound repair.

Purpose of the Study:

  • To investigate the impact of fibronectin polymerization on cell growth.
  • To determine if fibronectin matrix assembly is necessary for enhanced cell proliferation.
  • To differentiate the effects of fibronectin matrix assembly from integrin binding alone.

Main Methods:

  • Utilized fibronectin-null mouse embryonic cells cultured in serum-free conditions.
  • Assessed cell growth with and without exogenous fibronectin addition.

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  • Investigated the effect of inhibiting fibronectin matrix assembly.
  • Examined the role of Arg-Gly-Asp peptides and fibronectin fragments on integrin clustering and cell growth.

    • Main Results:

    • Fibronectin-null cells exhibited significantly increased adhesion-dependent growth (>2-5x) when cultured with exogenous fibronectin.
    • Inhibition of fibronectin matrix assembly blocked fibronectin-induced cell growth.
    • Arg-Gly-Asp peptides and fibronectin fragments promoted integrin clustering but did not enhance cell growth.

    Conclusions:

    • Fibronectin polymerization into the ECM is a positive regulator of cell growth.
    • Integrin binding and clustering are insufficient to stimulate increased cell growth without matrix assembly.
    • Fibronectin matrix assembly is a critical mechanism controlling cell proliferation.