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Cancer and Metastasis Reviews

, Volume 14, Issue 3, pp 173–189 | Cite as

Fibronectin and integrins in invasion and metastasis

  • Steven K. Akiyama
  • Kenneth Olden
  • Kenneth M. Yamada
Article

Summary

The adhesive glycoprotein fibronectin and integrin receptors appear to play important roles in the progression of metastatic disease. Fibronectin is a multifunctional extracellular glycoprotein that has at least two independent cell adhesion regions with different receptor specificities. The cell adhesive region in the central portion of fibronectin is comprised of at least two minimal amino acid sequences - an Arg-Gly-Asp (RGD) sequence and a Pro-His-Ser-Arg-Asn (PHSRN) sequence - which function in synergy. Another cell adhesive region is located near the carboxy-terminus in the alternatively spliced IIICS module. The critical minimal sequences for this region are Leu-Asp-Val (LDV) and Arg-Glu-Asp-Val (REDV) which function in an additive rather than synergistic fashion. Integrins are heterodimeric, transmembrane cell adhesion receptors for fibronectin and other extracellular matrix molecules. Several different integrins bind to fibronectin. The α5β1 fibronectin-specific integrin binds to the central RGD/PHSRN site. The α4β1 integrin binds to the IIICS site. Fibronectin-integrin interactions are important in tumor cell migration, invasion, and metastasis. In addition to promoting cell adhesion to the extracellular matrix, these proteins may also function in chemotaxis and control of proliferation. Peptide and antibody inhibitors of fibronectin and integrin functions have been shown to be effective inhibitors of metastasis, and are potentially important reagents for the study and control of cancer.

Key words

fibronectin integrins cell adhesion metastasis invasion 

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Copyright information

© Kluwer Academic Publishers 1995

Authors and Affiliations

  • Steven K. Akiyama
    • 1
  • Kenneth Olden
    • 2
  • Kenneth M. Yamada
    • 1
  1. 1.Laboratory of Developmental Biology, National Institute of Dental ResearchNational Institutes of HealthBethesdaUSA
  2. 2.Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health SciencesNational Institutes of HealthUSA

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