Bombesin induces angiogenesis and neuroblastoma growth.

Gastrin-releasing peptide (GRP), the mammalian equivalent of bombesin (BBS), is a trophic factor for highly vascular neuroblastomas; its mechanisms of action in vivo are unknown. We sought to determine the effects of BBS on the growth of neuroblastoma xenografts and on angiogenesis. BBS significantly increased the growth of SK-N-SH and BE(2)-C human neuroblastomas; tumors demonstrated increased expression of angiogenic markers, PECAM-1 and VEGF, as well as phosphorylated (p)-Akt levels. RC-3095, a BBS/GRP antagonist, attenuated BBS-stimulated tumor growth and angiogenesis in vivo. GRP or GRPR silencing significantly inhibited VEGF as well as p-Akt and p-mTOR expression in vitro. Our findings demonstrate that BBS stimulates neuroblastoma growth and the expression of angiogenic markers. Importantly, these findings suggest that novel therapeutic agents, targeting BBS-mediated angiogenesis, may be useful adjuncts in patients with advanced-stage neuroblastomas.