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Related Experiment Videos

Fibronectin polymerization stimulates cell growth by RGD-dependent and -independent mechanisms.

J Sottile1, D C Hocking, K J Langenbach

  • 1Department of Medicine, Center for Cardiovascular Research and Department of Pharmacology and Physiology, University of Rochester Medical Center, Box 679, Rochester, NY 14642, USA. jane_sottile@urmc. rochester.edu.

Journal of Cell Science
|November 9, 2000
PubMed
Summary

Fibronectin promotes cell growth independently of integrin binding through fibril formation. This process involves cell surface proteoglycans and is crucial for extracellular matrix interactions.

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Area of Science:

  • Cell Biology
  • Extracellular Matrix Biology
  • Biochemistry

Background:

  • Cell behavior, including migration and growth, is significantly influenced by interactions with the extracellular matrix (ECM).
  • Previous research demonstrated that soluble fibronectin enhances cell growth in fibronectin-null cells, contingent upon its deposition into the ECM, not just integrin engagement.

Purpose of the Study:

  • To investigate whether fibronectin's RGD (Arg-Gly-Asp) site is essential for its growth-promoting effects.
  • To elucidate the mechanism by which fibronectin influences cell growth, particularly the role of integrin binding and ECM deposition.

Main Methods:

  • Utilized fibronectin lacking the RGD site (FN(Delta)RGD) to assess its impact on cell growth.
  • Tested FN(Delta)RGD as both an adhesive substrate and in soluble form with collagen-adherent fibronectin-null cells.

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  • Employed inhibitors of fibronectin polymerization (anti-fibronectin antibody L8), heparin, heparitinase, and recombinant fibronectin heparin-binding domain to probe molecular interactions.
  • Assessed the effect of inhibitory β1 integrin antibodies on FN(Delta)RGD-induced effects.

    • Main Results:

    • FN(Delta)RGD significantly increased cell growth (1.6-1.8x) compared to controls, both as a substrate and in solution.
    • Inhibitors of fibronectin polymerization, heparin, and heparitinase treatment blocked FN(Delta)RGD-induced cell growth.
    • Heparin and heparitinase also partially inhibited wild-type fibronectin's growth-promoting effects and its ECM deposition.
    • FN(Delta)RGD fibril formation on the cell surface was inhibited by heparin and L8, but unaffected by β1 integrin antibodies.

    Conclusions:

    • Fibronectin promotes cell growth through a novel mechanism independent of RGD-integrin binding.
    • Fibronectin fibril formation and cell surface proteoglycans (heparan-sulfate proteoglycans) are key components in this growth-promoting pathway.
    • Integrin-independent fibronectin assembly plays a critical role in regulating cell growth via ECM interactions.