Fibronectin and integrins in invasion and metastasis.
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 lest 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 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 alpha 5 beta 1 fibronectin-specific integrin binds to the central RGD/PHSRN site. The alpha 4 beta 1 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.
Laboratory of Developmental Biology, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.
S K
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Akiyama
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K
Olden
K M
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Yamada
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D005353:Fibronectins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D016023:Integrins / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology*
D005353:Fibronectins; D016023:Integrins