Effects on in vitro and in vivo angiogenesis induced by small peptides carrying adhesion sequences

Maria Teresa Conconi, Francesca Ghezzo, Monica Dettin, Luca Urbani, Claudio Grandi, Diego Guidolin, Beatrice Nico, Carlo Di Bello, Domenico Ribatti, Pier Paolo Parnigotto

Research output: Contribution to journalArticle

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 RGDmotif mediating cell adhesion via integrin receptors [RGD, GRGDSPK, and (GRGDSP)4K] 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)4K 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) 4K. 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)4K seem to depend on its interaction with integrins, whereas the effects of HVP may be partially due to an impairment of HSPGs/FGF-2.

Original languageEnglish
Pages (from-to)349-357
Number of pages9
JournalJournal of Peptide Science
Volume16
Issue number7
DOIs
Publication statusPublished - 2010

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Keywords

  • Angiogenesis
  • Cell adhesion
  • FGF-2
  • Heparin-binding motif
  • RGD

ASJC Scopus subject areas

  • Structural Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Medicine(all)

Cite this

Conconi, M. T., Ghezzo, F., Dettin, M., Urbani, L., Grandi, C., Guidolin, D., Nico, B., Di Bello, C., Ribatti, D., & Parnigotto, P. P. (2010). Effects on in vitro and in vivo angiogenesis induced by small peptides carrying adhesion sequences. Journal of Peptide Science, 16(7), 349-357. https://doi.org/10.1002/psc.1251