The vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration

Daniela Belloni, Silvia Scabini, Chiara Foglieni, Lorenzo Veschini, Alessio Giazzon, Barbara Colombo, Alessandro Fulgenzi, Karen B Helle, Maria Elena Ferrero, Angelo Corti, Elisabetta Ferrero

Research output: Contribution to journalArticlepeer-review

74 Citations (Scopus)

Abstract

UNLABELLED: A growing body of evidence suggests that chromogranin A (CgA), a secretory protein released by many neuroendocrine cells and frequently used as a diagnostic and prognostic serum marker for a range of neuroendocrine tumors, is a precursor of several bioactive fragments. This work was undertaken to assess whether the N-terminal fragment CgA(1-76) (called vasostatin I) can inhibit the proangiogenic activity of vascular endothelial growth factor (VEGF), a factor involved in tumor growth. The effect of recombinant human vasostatin I (VS-1) on VEGF-induced human umbilical endothelial cells (HUVEC) signaling, proliferation, migration, and organization has been investigated. We have found that VS-1 (3 microg/ml; 330 nM) can inhibit VEGF-induced ERK phosphorylation, as well as cell migration, proliferation, morphogenesis, and invasion of collagen gels in various in vitro assays. In addition, VS-1 could inhibit the formation of capillary-like structures in Matrigel plugs in a rat model. VS-1 could also inhibit basal ERK phosphorylation and motility of HUVEC, leading to a more quiescent state in the absence of VEGF, without inducing apoptotic or necrotic effects.

CONCLUSION: These findings suggest that vasostatin I may play a novel role as a regulator of endothelial cell function and homeostasis.

Original languageEnglish
Pages (from-to)3052-62
Number of pages11
JournalFaseb Journal
Volume21
Issue number12
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Animals
  • Antigens, CD31
  • Cell Culture Techniques
  • Cell Line
  • Cell Movement
  • Cell Proliferation
  • Cell Shape
  • Chromogranin A
  • Collagen
  • Drug Combinations
  • Endothelial Cells
  • Extracellular Signal-Regulated MAP Kinases
  • Homeostasis
  • Humans
  • Laminin
  • Peptide Fragments
  • Phosphorylation
  • Proteoglycans
  • Rats
  • Rats, Inbred F344
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • von Willebrand Factor
  • Journal Article
  • Research Support, Non-U.S. Gov't

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