title: Effects on in vitro and in vivo angiogenesis induced by small peptides carrying adhesion sequences.
abstract: It is well known that tumor growth is strictly dependent on neo-vessel formation inside the tumor mass and that cell adhesion is required to allow EC proliferation and migration inside the tumor. In this work, we have evaluated the in vitro and in vivo effects on angiogenesis of some peptides, originally designed to promote cell adhesion on biomaterials, containing RGD motif mediating cell adhesion via integrin receptors [RGD, GRGDSPK, and (GRGDSP)(4)K] or the heparin-binding sequence of human vitronectin that interacts with HSPGs [HVP(351-359)]. Cell adhesion, proliferation, migration, and capillary-like tube formation in Matrigel were determined on HUVECs, whereas the effects on in vivo angiogenesis were evaluated using the CAM assay. (GRGDSP)(4)K linear sequence inhibited cell adhesion, decreased cell proliferation, migration and morphogenesis in Matrigel, and induced anti-angiogenic responses on CAM at higher degree than that determined after incubation with RGD or GRGDSPK. Moreover, it counteracted both in vitro and in vivo the pro-angiogenic effects induced by the Fibroblast growth factor (FGF-2). On the other hand, HVP was not able to affect cell adhesion and appeared less effective than (GRGDSP)(4)K. Our data indicate that the activity of RGD-containing peptides is related to their adhesive properties, and their effects are modulated by the number of cell adhesion motifs and the aminoacidic residues next to these sequences. The anti-angiogenic properties of (GRGDSP)(4)K seem to depend on its interaction with integrins, whereas the effects of HVP may be partially due to an impairment of HSPGs/FGF-2.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Padua, via Marzolo 5, 35131 Padua, Italy. mariateresa.conconi@unipd.it
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Conconi
authors.forename: Francesca
authors.initials: F
authors.lastname: Ghezzo
authors.forename: Monica
authors.initials: M
authors.lastname: Dettin
authors.forename: Luca
authors.initials: L
authors.lastname: Urbani
authors.forename: Claudio
authors.initials: C
authors.lastname: Grandi
authors.forename: Diego
authors.initials: D
authors.lastname: Guidolin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Nico
authors.forename: Carlo
authors.initials: C
authors.lastname: Di Bello
authors.forename: Domenico
authors.initials: D
authors.lastname: Ribatti
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Parnigotto
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D016023:Integrins; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016023:Integrins; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid