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.

The vasostatin-I fragment of chromogranin A inhibits VEGF-induced endothelial cell proliferation and migration / D. Belloni, S. Scabini, C. Foglieni, L. Veschini, A. Giazzon, B. Colombo, A. Fulgenzi, K.B. Helle, M.E. Ferrero, A. Corti, E. Ferrero. - In: THE FASEB JOURNAL. - ISSN 0892-6638. - 21:12(2007 Oct), pp. 3052-3062. [10.1096/fj.06-6829com]

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

D. Belloni
Primo
;
S. Scabini
Secondo
;
L. Veschini;A. Fulgenzi;M.E. Ferrero
Ultimo
;
2007

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 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.
Capillary-like structure; ERK/MAPK
Settore MED/04 - Patologia Generale
ott-2007
Article (author)
File in questo prodotto:
File Dimensione Formato  
faseb2007.pdf

accesso solo dalla rete interna

Tipologia: Publisher's version/PDF
Dimensione 649.03 kB
Formato Adobe PDF
649.03 kB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/37365
Citazioni
  • ???jsp.display-item.citation.pmc??? 21
  • Scopus 75
  • ???jsp.display-item.citation.isi??? 73
social impact