title: RGD peptides and monoclonal antibodies, antagonists of alpha(v)-integrin, enter the cells by independent endocytic pathways.
abstract: Cyclic synthetic peptides containing the arginine-glycine-aspartate motif (cRGD) and monoclonal antibodies (mAbs) targeted for individual integrins have been developed as potential therapeutic drugs for the treatment of several diseases. We showed that a cRGD peptide targeted for alpha(v)beta(3) was internalized in alpha(v)-integrin expressing and nonexpressing melanoma cells by an integrin independent fluid-phase endocytosis pathway that does not alter the number of functional integrin receptors at the cell surface. In contrast, a blocking mAb directed to alpha(v) was internalized by an integrin-dependent endocytosis pathway that reduced the number of functional integrin receptors at the cell surface. We prove that melanoma cells pretreated with the mAb do not readhere to the substrate, whereas cells pretreated with cRGD peptide retain their readhesion capacity. Given the growing importance of RGD peptides, knowledge of these cellular mechanisms is required to improve the development of antiangiogenic and anti-inflammatory drugs.
authors.affiliation: Departament de Biologia Cellular, Universitat de Barcelona, Barcelona, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Castel
authors.forename: R
authors.initials: R
authors.lastname: Pagan
authors.forename: F
authors.initials: F
authors.lastname: Mitjans
authors.forename: J
authors.initials: J
authors.lastname: Piulats
authors.forename: S
authors.initials: S
authors.lastname: Goodman
authors.forename: A
authors.initials: A
authors.lastname: Jonczyk
authors.forename: F
authors.initials: F
authors.lastname: Huber
authors.forename: S
authors.initials: S
authors.lastname: Vilaró
authors.forename: M
authors.initials: M
authors.lastname: Reina
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism*; D015703:Antigens, CD / Q000276:immunology*; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D006801:Humans; D039564:Integrin alphaV; D016023:Integrins / Q000502:physiology; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000502:physiology; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D039564:Integrin alphaV; D016023:Integrins; D009842:Oligopeptides; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid