title: Ganglioside GT1b inhibits keratinocyte adhesion and migration on a fibronectin matrix.
abstract: Highly sialylated gangliosides have been shown to alter cellular adhesion to a fibronectin matrix. The effect of these gangliosides on the adhesion, spreading, and migration of cultured keratinocytes on a fibronectin matrix has not been explored. Ganglioside GT1b significantly prevented attachment of keratinocytes to fibronectin and also detached previously adherent keratinocytes in a concentration-dependent manner without cell toxicity. GT1b did not affect adhesion of keratinocytes to wells coated with laminin, type I or type IV collagen, 804G extracellular matrix, or albumin. GT1b also inhibited keratinocyte migration on fibronectin in a concentration-dependent manner at concentrations as low as 5 nM GT1b, but had no effect on migration of keratinocytes plated on other matrices. GT1b binds to intact fibronectin and to the 120-kD RGDS-containing cell-binding fibronectin fragment, but not to the heparin- or gelatin-binding fragments of fibronectin. Although RGDS competes with GT1b in inhibiting adhesion, GT1b does not diminish binding of keratinocytes to a derivatized RGDS substratum, suggesting that the GT1b effect involves a non-RGDS site in the cell-binding region that modulates RGDS/alpha 5 beta 1 integrin receptor interaction. Through a specific effect on keratinocyte interaction with fibronectin, GT1b may participate in the regulation of cell adhesion and migration on a fibronectin substratum, which are important events during wound healing and the spreading of cutaneous neoplasia.
authors.affiliation: Department of Pediatrics, Northwestern University Medical School, Chicago, Illinois, USA.
authors.forename: A S
authors.initials: AS
authors.lastname: Paller
authors.forename: S L
authors.initials: SL
authors.lastname: Arnsmeier
authors.forename: J D
authors.initials: JD
authors.lastname: Chen
authors.forename: D T
authors.initials: DT
authors.lastname: Woodley
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005340:Fibrinogen / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D005353:Fibronectins; D005732:Gangliosides; D009842:Oligopeptides; D010446:Peptide Fragments; C016481:trisialoganglioside GT1; D005340:Fibrinogen; C046617:arginyl-glycyl-aspartyl-serine