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 journalArticle

Abstract

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 CgA1-76 (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 μg/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)3052-3062
Number of pages11
JournalFASEB Journal
Volume21
Issue number12
DOIs
Publication statusPublished - Oct 2007

Keywords

  • Capillary-like structure
  • ERK/MAPK

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology
  • Medicine(all)

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  • Cite this

    Belloni, D., Scabini, S., Foglieni, C., Veschini, L., Giazzon, A., Colombo, B., Fulgenzi, A., Helle, K. B., Ferrero, M. E., Corti, A., & Ferrero, E. (2007). The vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration. FASEB Journal, 21(12), 3052-3062. https://doi.org/10.1096/fj.06-6829com