Bombesin induces angiogenesis and neuroblastoma growth

Jung Hee Kang, Titilope A. Ishola, Naira Baregamian, Joshua M. Mourot, Piotr G. Rychahou, B. Mark Evers, Dai H. Chung

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)273-281
Number of pages9
JournalCancer Letters
Volume253
Issue number2
DOIs
StatePublished - Aug 18 2007
Externally publishedYes

Keywords

  • Angiogenesis
  • Bombesin
  • GRP
  • Neuroblastoma
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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