title: The high affinity heparin-binding domain and the V region of fibronectin mediate invasion of human oral squamous cell carcinoma cells in vitro.
abstract: Fibronectin is an extracellular matrix molecule composed of repeating subunits that create functional domains. These domains contain multiple binding sites for heparin and for various cell-surface receptors that modulate cell function. To examine the role that the high affinity heparin-binding region and the alternatively spliced V region of fibronectin play in tumor invasion, we expressed and purified four complementary recombinant fibronectin proteins. These proteins either included or excluded the alternatively spliced V region and contained either a mutated, non-functional high affinity heparin-binding domain (Hep-) or an unmutated heparin-binding domain (Hep+). Cultured oral squamous cell carcinoma cells were assayed for invasion into a Matrigel/collagen matrix supplemented with these four purified recombinant proteins, and for spreading and motility on plastic. Increased invasion was observed in gels supplemented with the V-Hep+ protein when compared with the V-Hep- protein. Inclusion of the V region in the proteins enhanced the invasion and migration associated with both Hep+ and Hep- proteins, whereas cell spreading was enhanced with the Hep+ recombinant proteins. These data demonstrate that both the high affinity heparin-binding domain and the V region of fibronectin play important roles in invasion, motility, and spreading of oral squamous cell carcinoma cells.
authors.affiliation: Department of Stomatology, School of Dentistry, University of California, San Francisco, California 94143-0650, USA.
authors.forename: Y L
authors.initials: YL
authors.lastname: Kapila
authors.forename: J
authors.initials: J
authors.lastname: Niu
authors.forename: P W
authors.initials: PW
authors.lastname: Johnson
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001672:Biocompatible Materials; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D003094:Collagen; D004338:Drug Combinations; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D007797:Laminin; D008969:Molecular Sequence Data; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D011509:Proteoglycans; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D011509:Proteoglycans; D011994:Recombinant Proteins; C059485:matrigel; D006493:Heparin; D003094:Collagen