title: Single-domain antibodies that compete with the natural ligand fibroblast growth factor block the internalization of the fibroblast growth factor receptor 1.
abstract: Single-domain antibodies in VHH format specific for fibroblast growth factor receptor 1 (FGFR1) were isolated from a phage-display llama naïve library. In particular, phage elution in the presence of the natural receptor ligand fibroblast growth factor (FGF) allowed for the identification of recombinant antibodies that compete with FGF for the same region on the receptor surface. These antibodies posses a relatively low affinity for FGFR1 and were never identified when unspecific elution conditions favoring highly affine binders were applied to panning procedures. Two populations of competitive antibodies were identified that labeled specifically the receptor-expressing cells in immunofluorescence and recognize distinct epitopes. Antibodies from both populations effectively prevented FGF-dependent internalization and nuclear accumulation of the receptor in cultured cells. This achievement indicates that these antibodies have a capacity to modulate the receptor physiology and, therefore, constitute powerful reagents for basic research and a potential lead for therapeutic applications.
authors.affiliation: IFOM-IEO Campus, Via Adamello 16, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Veggiani
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ossolengo
authors.forename: Marisa
authors.initials: M
authors.lastname: Aliprandi
authors.forename: Ugo
authors.initials: U
authors.lastname: Cavallaro
authors.forename: Ario
authors.initials: A
authors.lastname: de Marco
mesh_terms: D000906:Antibodies / Q000302:isolation & purification / Q000494:pharmacology*; D002467:Cell Nucleus / Q000201:enzymology; D005346:Fibroblast Growth Factors / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D019151:Peptide Library; D017434:Protein Structure, Tertiary; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000906:Antibodies; D008024:Ligands; D019151:Peptide Library; D005346:Fibroblast Growth Factors; D051496:Receptor, Fibroblast Growth Factor, Type 1