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


CONCLUSIONS
These findings suggest that vasostatin I may play a novel role as a regulator of endothelial cell function and homeostasis.
Belloni
Daniela
D
Department of Oncology and IIT Network Research Unit of Molecular Neurosciences, DIBIT, San Raffaele H Scientific Institute, Via Olgettina 60, 20132 Milan, Italy.
Scabini
Silvia
S
Foglieni
Chiara
C
Veschini
Lorenzo
L
Giazzon
Alessio
A
Colombo
Barbara
B
Fulgenzi
Alessandro
A
Helle
Karen B
KB
Ferrero
Maria Elena
ME
Corti
Angelo
A
Ferrero
Elisabetta
E
D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D053379:Chromogranin A / Q000235:genetics / Q000378:metabolism*; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007797:Laminin; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011509:Proteoglycans; D051381:Rats; D011916:Rats, Inbred F344; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
D053379:Chromogranin A; D004338:Drug Combinations; D007797:Laminin; D010446:Peptide Fragments; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D011509:Proteoglycans; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D014841:von Willebrand Factor; C059485:matrigel; C064110:vasostatin I; D003094:Collagen; D048049:Extracellular Signal-Regulated MAP Kinases