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

Abstract

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 recom‐binant 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.—Belloni, D., Scabini, S., Foglieni, C., Veschini, L., Giazzon, A., Colombo, B., Fulgenzi, A., Helle, K. B., Ferrero, M. E., Corti, A., Ferrero, E. The vasostatin‐I fragment of chromogranin A inhibits VEGF‐induced endothelial cell proliferation and migration. FASEB J. 21, 3052–3062 (2007)